Analysis of mutant DNA polymerase γ in patients with mitochondrial DNA depletion
We studied six unrelated children with depletion of mitochondrial DNA (mtDNA). They presented with Leigh syndrome, infantile hepatocerebral mtDNA depletion syndrome, or Alpers-Huttenlocher syndrome. Several genes have been implicated in mtDNA depletion. Screening of candidate genes indicated that al...
Saved in:
| Published in | Human mutation Vol. 30; no. 2; pp. 248 - 254 |
|---|---|
| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.02.2009
|
| Subjects | |
| Online Access | Get full text |
| ISSN | 1059-7794 1098-1004 1098-1004 |
| DOI | 10.1002/humu.20852 |
Cover
| Abstract | We studied six unrelated children with depletion of mitochondrial DNA (mtDNA). They presented with Leigh syndrome, infantile hepatocerebral mtDNA depletion syndrome, or Alpers-Huttenlocher syndrome. Several genes have been implicated in mtDNA depletion. Screening of candidate genes indicated that all six patients were compound heterozygous for missense mutations in the gene for the catalytic subunit of DNA polymerase γ (POLG). Three of the identified mutations, c.3328C>T (p.H1110Y), c.3401A>G (p.H1134R), and c.3406G>A (p.E1136K), have not been reported earlier. To investigate the functional consequences of the mutations, we carried out a series of biochemical assays in cultured fibroblasts. These studies revealed that fibroblast cultures from the patients with infantile hepatocerebral mtDNA depletion syndrome progressively lost their mtDNA during culturing, whereas fibroblast cultures from patients presenting with Leigh syndrome or Alpers-Huttenlocher syndrome had reduced but stable levels of mtDNA. DNA polymerase γ activity was below the normal range in all patient cultures, except for one; however, this culture showed low levels of the heterodimeric enzyme and poor DNA polymerase γ processivity. Parental fibroblast cultures had normal catalytic efficiency of DNA polymerase γ, consistent with the observation that all carriers are asymptomatic. Thus, we report the first patient with Leigh syndrome caused by POLG mutations. The cell culture experiments established the pathogenicity of the identified POLG mutations and helped to define the molecular mechanisms responsible for mtDNA depletion in the patients' tissues. The assays may facilitate the identification of those patients in whom screening for POLG mutations would be most appropriate. Hum Mutat 0, 1-8, 2008. |
|---|---|
| AbstractList | We studied six unrelated children with depletion of mitochondrial DNA (mtDNA). They presented with Leigh syndrome, infantile hepatocerebral mtDNA depletion syndrome, or Alpers-Huttenlocher syndrome. Several genes have been implicated in mtDNA depletion. Screening of candidate genes indicated that all six patients were compound heterozygous for missense mutations in the gene for the catalytic subunit of DNA polymerase gamma (POLG). Three of the identified mutations, c.3328C>T (p.H1110Y), c.3401A>G (p.H1134R), and c.3406G>A (p.E1136K), have not been reported earlier. To investigate the functional consequences of the mutations, we carried out a series of biochemical assays in cultured fibroblasts. These studies revealed that fibroblast cultures from the patients with infantile hepatocerebral mtDNA depletion syndrome progressively lost their mtDNA during culturing, whereas fibroblast cultures from patients presenting with Leigh syndrome or Alpers-Huttenlocher syndrome had reduced but stable levels of mtDNA. DNA polymerase gamma activity was below the normal range in all patient cultures, except for one; however, this culture showed low levels of the heterodimeric enzyme and poor DNA polymerase gamma processivity. Parental fibroblast cultures had normal catalytic efficiency of DNA polymerase gamma, consistent with the observation that all carriers are asymptomatic. Thus, we report the first patient with Leigh syndrome caused by POLG mutations. The cell culture experiments established the pathogenicity of the identified POLG mutations and helped to define the molecular mechanisms responsible for mtDNA depletion in the patients' tissues. The assays may facilitate the identification of those patients in whom screening for POLG mutations would be most appropriate.We studied six unrelated children with depletion of mitochondrial DNA (mtDNA). They presented with Leigh syndrome, infantile hepatocerebral mtDNA depletion syndrome, or Alpers-Huttenlocher syndrome. Several genes have been implicated in mtDNA depletion. Screening of candidate genes indicated that all six patients were compound heterozygous for missense mutations in the gene for the catalytic subunit of DNA polymerase gamma (POLG). Three of the identified mutations, c.3328C>T (p.H1110Y), c.3401A>G (p.H1134R), and c.3406G>A (p.E1136K), have not been reported earlier. To investigate the functional consequences of the mutations, we carried out a series of biochemical assays in cultured fibroblasts. These studies revealed that fibroblast cultures from the patients with infantile hepatocerebral mtDNA depletion syndrome progressively lost their mtDNA during culturing, whereas fibroblast cultures from patients presenting with Leigh syndrome or Alpers-Huttenlocher syndrome had reduced but stable levels of mtDNA. DNA polymerase gamma activity was below the normal range in all patient cultures, except for one; however, this culture showed low levels of the heterodimeric enzyme and poor DNA polymerase gamma processivity. Parental fibroblast cultures had normal catalytic efficiency of DNA polymerase gamma, consistent with the observation that all carriers are asymptomatic. Thus, we report the first patient with Leigh syndrome caused by POLG mutations. The cell culture experiments established the pathogenicity of the identified POLG mutations and helped to define the molecular mechanisms responsible for mtDNA depletion in the patients' tissues. The assays may facilitate the identification of those patients in whom screening for POLG mutations would be most appropriate. We studied six unrelated children with depletion of mitochondrial DNA (mtDNA). They presented with Leigh syndrome, infantile hepatocerebral mtDNA depletion syndrome, or Alpers-Huttenlocher syndrome. Several genes have been implicated in mtDNA depletion. Screening of candidate genes indicated that all six patients were compound heterozygous for missense mutations in the gene for the catalytic subunit of DNA polymerase (POLG). Three of the identified mutations, c.3328C>T (p.H1110Y), c.3401A>G (p.H1134R), and c.3406G>A (p.E1136K), have not been reported earlier. To investigate the functional consequences of the mutations, we carried out a series of biochemical assays in cultured fibroblasts. These studies revealed that fibroblast cultures from the patients with infantile hepatocerebral mtDNA depletion syndrome progressively lost their mtDNA during culturing, whereas fibroblast cultures from patients presenting with Leigh syndrome or Alpers-Huttenlocher syndrome had reduced but stable levels of mtDNA. DNA polymerase activity was below the normal range in all patient cultures, except for one; however, this culture showed low levels of the heterodimeric enzyme and poor DNA polymerase processivity. Parental fibroblast cultures had normal catalytic efficiency of DNA polymerase , consistent with the observation that all carriers are asymptomatic. Thus, we report the first patient with Leigh syndrome caused by POLG mutations. The cell culture experiments established the pathogenicity of the identified POLG mutations and helped to define the molecular mechanisms responsible for mtDNA depletion in the patients' tissues. The assays may facilitate the identification of those patients in whom screening for POLG mutations would be most appropriate. Hum Mutat 0, 1-8, 2008. We studied six unrelated children with depletion of mitochondrial DNA (mtDNA). They presented with Leigh syndrome, infantile hepatocerebral mtDNA depletion syndrome, or Alpers-Huttenlocher syndrome. Several genes have been implicated in mtDNA depletion. Screening of candidate genes indicated that all six patients were compound heterozygous for missense mutations in the gene for the catalytic subunit of DNA polymerase gamma (POLG). Three of the identified mutations, c.3328C>T (p.H1110Y), c.3401A>G (p.H1134R), and c.3406G>A (p.E1136K), have not been reported earlier. To investigate the functional consequences of the mutations, we carried out a series of biochemical assays in cultured fibroblasts. These studies revealed that fibroblast cultures from the patients with infantile hepatocerebral mtDNA depletion syndrome progressively lost their mtDNA during culturing, whereas fibroblast cultures from patients presenting with Leigh syndrome or Alpers-Huttenlocher syndrome had reduced but stable levels of mtDNA. DNA polymerase gamma activity was below the normal range in all patient cultures, except for one; however, this culture showed low levels of the heterodimeric enzyme and poor DNA polymerase gamma processivity. Parental fibroblast cultures had normal catalytic efficiency of DNA polymerase gamma , consistent with the observation that all carriers are asymptomatic. Thus, we report the first patient with Leigh syndrome caused by POLG mutations. The cell culture experiments established the pathogenicity of the identified POLG mutations and helped to define the molecular mechanisms responsible for mtDNA depletion in the patients' tissues. The assays may facilitate the identification of those patients in whom screening for POLG mutations would be most appropriate. Hum Mutat 0, 1-8, 2008. We studied six unrelated children with depletion of mitochondrial DNA (mtDNA). They presented with Leigh syndrome, infantile hepatocerebral mtDNA depletion syndrome, or Alpers‐Huttenlocher syndrome. Several genes have been implicated in mtDNA depletion. Screening of candidate genes indicated that all six patients were compound heterozygous for missense mutations in the gene for the catalytic subunit of DNA polymerase γ (POLG). Three of the identified mutations, c.3328C>T (p.H1110Y), c.3401A>G (p.H1134R), and c.3406G>A (p.E1136K), have not been reported earlier. To investigate the functional consequences of the mutations, we carried out a series of biochemical assays in cultured fibroblasts. These studies revealed that fibroblast cultures from the patients with infantile hepatocerebral mtDNA depletion syndrome progressively lost their mtDNA during culturing, whereas fibroblast cultures from patients presenting with Leigh syndrome or Alpers‐Huttenlocher syndrome had reduced but stable levels of mtDNA. DNA polymerase γ activity was below the normal range in all patient cultures, except for one; however, this culture showed low levels of the heterodimeric enzyme and poor DNA polymerase γ processivity. Parental fibroblast cultures had normal catalytic efficiency of DNA polymerase γ, consistent with the observation that all carriers are asymptomatic. Thus, we report the first patient with Leigh syndrome caused by POLG mutations. The cell culture experiments established the pathogenicity of the identified POLG mutations and helped to define the molecular mechanisms responsible for mtDNA depletion in the patients' tissues. The assays may facilitate the identification of those patients in whom screening for POLG mutations would be most appropriate. Hum Mutat 0, 1–8, 2008. © 2008 Wiley‐Liss, Inc. We studied six unrelated children with depletion of mitochondrial DNA (mtDNA). They presented with Leigh syndrome, infantile hepatocerebral mtDNA depletion syndrome, or Alpers-Huttenlocher syndrome. Several genes have been implicated in mtDNA depletion. Screening of candidate genes indicated that all six patients were compound heterozygous for missense mutations in the gene for the catalytic subunit of DNA polymerase γ (POLG). Three of the identified mutations, c.3328C>T (p.H1110Y), c.3401A>G (p.H1134R), and c.3406G>A (p.E1136K), have not been reported earlier. To investigate the functional consequences of the mutations, we carried out a series of biochemical assays in cultured fibroblasts. These studies revealed that fibroblast cultures from the patients with infantile hepatocerebral mtDNA depletion syndrome progressively lost their mtDNA during culturing, whereas fibroblast cultures from patients presenting with Leigh syndrome or Alpers-Huttenlocher syndrome had reduced but stable levels of mtDNA. DNA polymerase γ activity was below the normal range in all patient cultures, except for one; however, this culture showed low levels of the heterodimeric enzyme and poor DNA polymerase γ processivity. Parental fibroblast cultures had normal catalytic efficiency of DNA polymerase γ, consistent with the observation that all carriers are asymptomatic. Thus, we report the first patient with Leigh syndrome caused by POLG mutations. The cell culture experiments established the pathogenicity of the identified POLG mutations and helped to define the molecular mechanisms responsible for mtDNA depletion in the patients' tissues. The assays may facilitate the identification of those patients in whom screening for POLG mutations would be most appropriate. Hum Mutat 0, 1-8, 2008. We studied six unrelated children with depletion of mitochondrial DNA (mtDNA). They presented with Leigh syndrome, infantile hepatocerebral mtDNA depletion syndrome, or Alpers-Huttenlocher syndrome. Several genes have been implicated in mtDNA depletion. Screening of candidate genes indicated that all six patients were compound heterozygous for missense mutations in the gene for the catalytic subunit of DNA polymerase gamma (POLG). Three of the identified mutations, c.3328C>T (p.H1110Y), c.3401A>G (p.H1134R), and c.3406G>A (p.E1136K), have not been reported earlier. To investigate the functional consequences of the mutations, we carried out a series of biochemical assays in cultured fibroblasts. These studies revealed that fibroblast cultures from the patients with infantile hepatocerebral mtDNA depletion syndrome progressively lost their mtDNA during culturing, whereas fibroblast cultures from patients presenting with Leigh syndrome or Alpers-Huttenlocher syndrome had reduced but stable levels of mtDNA. DNA polymerase gamma activity was below the normal range in all patient cultures, except for one; however, this culture showed low levels of the heterodimeric enzyme and poor DNA polymerase gamma processivity. Parental fibroblast cultures had normal catalytic efficiency of DNA polymerase gamma, consistent with the observation that all carriers are asymptomatic. Thus, we report the first patient with Leigh syndrome caused by POLG mutations. The cell culture experiments established the pathogenicity of the identified POLG mutations and helped to define the molecular mechanisms responsible for mtDNA depletion in the patients' tissues. The assays may facilitate the identification of those patients in whom screening for POLG mutations would be most appropriate. |
| Author | Bitner-Glindzicz, Maria Rahman, Shamima Leonard, James V Schapira, Anthony H.V Pagnamenta, Alistair T Taanman, Jan-Willem Morris, Andrew A.M Wolf, Nicole I Clayton, Peter T |
| Author_xml | – sequence: 1 fullname: Taanman, Jan-Willem – sequence: 2 fullname: Rahman, Shamima – sequence: 3 fullname: Pagnamenta, Alistair T – sequence: 4 fullname: Morris, Andrew A.M – sequence: 5 fullname: Bitner-Glindzicz, Maria – sequence: 6 fullname: Wolf, Nicole I – sequence: 7 fullname: Leonard, James V – sequence: 8 fullname: Clayton, Peter T – sequence: 9 fullname: Schapira, Anthony H.V |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/18828154$$D View this record in MEDLINE/PubMed |
| BookMark | eNqFksuKFDEUhoOMOBfd-ACalYhQY65VybIZLyOMimivQyqV2JFUUpOkGPq5fA-fyerpHgSRcXXC4fv-xflzCo5iihaApxidY4TI6808zucECU4egBOMpGiWNTvavblsuk6yY3Bayg-EFobTR-AYC0EE5uwEfFlFHbbFF5gcHOeqY4VvPq3glMJ2tFkXC3_9hD7CSVdvYy3wxtcNHH1NZpPikL0Ot8Jgp2CrT_ExeOh0KPbJYZ6B9bu33y4um6vP7z9crK4awzAnDe14K5EeDO2NQL0wSBgn5WCka4klDElLhx47x0nbMYYxMQS7QTstDe16Qc_Ai33ulNP1bEtVoy_GhqCjTXNRbSsEooT_FySIc9m1bAFf3gvirmtbfsh8dkDnfrSDmrIfdd6qu8MuwKs9YHIqJVv3B0Fq15rataZuW1tg9BdsfNW7Y9asffi3gvfKjQ92e0-4ulx_XN85z_eO00np79kXtf5KEKYIc7n8G0Z_A1bHsuU |
| CitedBy_id | crossref_primary_10_1074_jbc_M109_011940 crossref_primary_10_1016_j_mito_2018_11_004 crossref_primary_10_3390_biomedicines11041172 crossref_primary_10_1002_msj_20303 crossref_primary_10_1091_mbc_e09_04_0296 crossref_primary_10_3389_fgene_2021_664278 crossref_primary_10_1016_j_nmd_2021_01_004 crossref_primary_10_1093_hmg_ddt094 crossref_primary_10_1016_j_nmd_2015_01_004 crossref_primary_10_1016_j_bbadis_2023_166786 crossref_primary_10_1038_nrneurol_2010_52 crossref_primary_10_1002_lt_23965 crossref_primary_10_1016_j_mito_2010_07_011 crossref_primary_10_1016_j_bbadis_2010_11_012 crossref_primary_10_1186_s13023_020_1297_9 crossref_primary_10_1111_epi_13508 crossref_primary_10_1007_s00415_011_6268_6 crossref_primary_10_1097_NEN_0000000000000195 crossref_primary_10_4061_2011_159160 crossref_primary_10_1111_ahg_12111 crossref_primary_10_1016_j_tcb_2014_11_002 crossref_primary_10_1111_j_1469_8749_2011_04214_x crossref_primary_10_1016_j_dnarep_2014_03_010 crossref_primary_10_1016_S0140_6736_11_61305_6 crossref_primary_10_1212_WNL_0b013e3181df099f crossref_primary_10_1002_jimd_12211 crossref_primary_10_1002_ana_24551 crossref_primary_10_1016_j_pediatrneurol_2012_09_014 crossref_primary_10_3389_fgene_2015_00106 crossref_primary_10_1002_ddrr_105 crossref_primary_10_1016_j_ymeth_2010_03_002 crossref_primary_10_1007_s00018_010_0530_4 crossref_primary_10_12659_MSM_881716 crossref_primary_10_1093_hmg_ddv509 crossref_primary_10_1016_j_ymgme_2015_12_004 crossref_primary_10_1111_j_1399_0012_2009_01203_x crossref_primary_10_1093_brain_aws231 crossref_primary_10_1038_ejhg_2013_171 |
| Cites_doi | 10.1093/hmg/ddl424 10.1016/j.jmb.2006.02.073 10.1016/S1046-2023(02)00038-5 10.1074/jbc.M506762200 10.1021/bi980772w 10.1093/hmg/ddm227 10.1093/oxfordjournals.jbchem.a132139 10.1016/j.bbadis.2007.10.002 10.1086/430843 10.1074/jbc.M509730200 10.1093/brain/awh410 10.1002/j.1460-2075.1992.tb05337.x 10.1038/nsmb805 10.1021/cr040463d 10.1126/science.2814477 10.1016/S0014-4827(03)00249-0 10.1093/nar/26.19.4365 10.1038/ng746 10.1093/hmg/ddi196 10.1074/jbc.274.53.38197 10.1002/ana.20079 10.1093/clinchem/45.10.1725 10.1038/90034 10.1042/bj3050817 10.1016/S0002-9440(10)65100-0 10.1093/humrep/del076 10.1146/annurev.bi.60.070191.002501 10.1002/ana.21207 10.1038/ng1765 10.1093/hmg/ddl219 10.1016/S0021-9258(18)42629-4 10.1093/hmg/ddi454 10.1038/sj.emboj.7601843 |
| ContentType | Journal Article |
| Copyright | 2008 Wiley‐Liss, Inc. (c) 2008 Wiley-Liss, Inc. |
| Copyright_xml | – notice: 2008 Wiley‐Liss, Inc. – notice: (c) 2008 Wiley-Liss, Inc. |
| DBID | FBQ AAYXX CITATION CGR CUY CVF ECM EIF NPM 7TM 8FD FR3 P64 RC3 7X8 |
| DOI | 10.1002/humu.20852 |
| DatabaseName | AGRIS CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Nucleic Acids Abstracts Technology Research Database Engineering Research Database Biotechnology and BioEngineering Abstracts Genetics Abstracts MEDLINE - Academic |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Genetics Abstracts Engineering Research Database Technology Research Database Nucleic Acids Abstracts Biotechnology and BioEngineering Abstracts MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic Genetics Abstracts Genetics Abstracts MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database – sequence: 3 dbid: FBQ name: AGRIS url: http://www.fao.org/agris/Centre.asp?Menu_1ID=DB&Menu_2ID=DB1&Language=EN&Content=http://www.fao.org/agris/search?Language=EN sourceTypes: Publisher |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine Biology |
| EISSN | 1098-1004 |
| EndPage | 254 |
| ExternalDocumentID | 18828154 10_1002_humu_20852 HUMU20852 US201301591094 |
| Genre | article Research Support, Non-U.S. Gov't Journal Article |
| GrantInformation_xml | – fundername: The Wellcome Trust funderid: 048410 – fundername: Child Health Research Appeal Trust – fundername: Medical Research Council, and the National Health Service Executive – fundername: Children Living with Inherited Metabolic Diseases – fundername: Medical Research Council grantid: G0601943 – fundername: Medical Research Council grantid: G0200335 – fundername: Wellcome Trust grantid: 048410 |
| GroupedDBID | --- .3N .55 .GA .Y3 05W 0R~ 10A 169 1L6 1OB 1OC 1ZS 29I 31~ 33P 3SF 3V. 3WU 4.4 4ZD 50Y 50Z 51W 51X 52M 52N 52O 52P 52S 52T 52U 52W 52X 53G 5GY 5VS 66C 702 7PT 7X7 8-0 8-1 8-3 8-4 8-5 88A 88E 8C1 8FE 8FH 8FI 8FJ 8R4 8R5 8UM 930 A03 AAESR AAEVG AAHHS AAJEY AAONW AASGY AAXRX AAZKR ABCQN ABCUV ABEML ABHUG ABIJN ABJNI ABPVW ABUWG ABWRO ACAHQ ACBWZ ACCFJ ACCZN ACFBH ACGFS ACPOU ACPRK ACSCC ACXBN ACXME ACXQS ADAWD ADBBV ADDAD ADEOM ADIZJ ADKYN ADMGS ADOZA ADXAS ADZMN ADZOD AEEZP AEIMD AENEX AEQDE AEQTP AEUQT AFBPY AFGKR AFKRA AFPWT AFVGU AFZJQ AGJLS AHMBA AIURR AIWBW AJAOE AJBDE AJXKR ALAGY ALMA_UNASSIGNED_HOLDINGS AMBMR AMYDB ASPBG ATUGU AUFTA AVWKF AZBYB AZFZN AZVAB BAFTC BBNVY BDRZF BENPR BFHJK BHBCM BHPHI BMNLL BMXJE BNHUX BPHCQ BROTX BRXPI BVXVI BY8 C45 CCPQU CS3 D-E D-F DCZOG DPXWK DR2 DRFUL DRSTM DU5 DVXWH EBD EBS EJD EMOBN F00 F01 F04 F5P FBQ FEDTE FYUFA G-S G.N GNP GODZA H.T H.X HBH HCIFZ HF~ HHY HHZ HMCUK HVGLF HZ~ IX1 J0M JPC KQQ LATKE LAW LC2 LC3 LEEKS LH4 LITHE LK8 LOXES LP6 LP7 LUTES LW6 LYRES M0L M1P M66 M7P MEWTI MK4 MRFUL MRSTM MSFUL MSSTM MXFUL MXSTM N04 N05 N9A NF~ NNB O66 O9- OVD P2P P2W P2X P4D PALCI PIMPY PQQKQ PROAC PSQYO Q.N Q11 Q2X QB0 QRW R.K RHX RIWAO RJQFR ROL RWI RWV RX1 RYL SAMSI SUPJJ SV3 TEORI UB1 UDS UKHRP V2E W8V W99 WBKPD WIB WIH WIK WJL WNSPC WOHZO WQJ WRC WTM WXSBR WYISQ X7M XG1 XSW XV2 ZZTAW ~IA ~KM ~WT 24P AANHP ACCMX ACRPL ACYXJ ADNMO ALIPV ALUQN H13 OIG AAMMB AAYXX AEFGJ AGQPQ AGXDD AIDQK AIDYY AIQQE CITATION PHGZM PHGZT PJZUB PPXIY PQGLB PUEGO RPM CGR CUY CVF ECM EIF NPM 7TM 8FD FR3 P64 RC3 7X8 |
| ID | FETCH-LOGICAL-c4152-375690adc3bc80b8c08cf99dc9f62e2409e3db1ff526744112c21fdafa9c37b83 |
| IEDL.DBID | DR2 |
| ISSN | 1059-7794 1098-1004 |
| IngestDate | Wed Oct 01 13:30:00 EDT 2025 Wed Oct 01 14:18:09 EDT 2025 Thu Sep 04 15:18:13 EDT 2025 Mon Jul 21 05:47:11 EDT 2025 Thu Apr 24 23:06:55 EDT 2025 Wed Oct 01 01:56:23 EDT 2025 Wed Jan 22 16:40:28 EST 2025 Wed Dec 27 19:15:42 EST 2023 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 2 |
| Language | English |
| License | http://doi.wiley.com/10.1002/tdm_license_1.1 (c) 2008 Wiley-Liss, Inc. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c4152-375690adc3bc80b8c08cf99dc9f62e2409e3db1ff526744112c21fdafa9c37b83 |
| Notes | http://dx.doi.org/10.1002/humu.20852 Communicated by David S. Rosenblatt ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| PMID | 18828154 |
| PQID | 1776650325 |
| PQPubID | 23462 |
| PageCount | 7 |
| ParticipantIDs | proquest_miscellaneous_66880325 proquest_miscellaneous_20559764 proquest_miscellaneous_1776650325 pubmed_primary_18828154 crossref_primary_10_1002_humu_20852 crossref_citationtrail_10_1002_humu_20852 wiley_primary_10_1002_humu_20852_HUMU20852 fao_agris_US201301591094 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | February 2009 |
| PublicationDateYYYYMMDD | 2009-02-01 |
| PublicationDate_xml | – month: 02 year: 2009 text: February 2009 |
| PublicationDecade | 2000 |
| PublicationPlace | Hoboken |
| PublicationPlace_xml | – name: Hoboken – name: United States |
| PublicationTitle | Human mutation |
| PublicationTitleAlternate | Hum Mutat |
| PublicationYear | 2009 |
| Publisher | Wiley Subscription Services, Inc., A Wiley Company |
| Publisher_xml | – name: Wiley Subscription Services, Inc., A Wiley Company |
| References | 1998; 26 2006; 38 1992; 267 2006; 15 1999; 45 1991; 60 2001; 28 2001; 29 2006; 358 1992; 11 2007; 16 2004; 11 1998; 37 2004; 55 2005; 280 2002; 26 1989; 246 2006; 21 1978; 84 2007; 1772 2005; 128 1995; 305 1999; 274 1987 2005; 76 1999; 155 2007; 62 2006; 281 2003; 289 2006; 106 2007; 26 2005; 14 Nijtmans (10.1002/humu.20852-BIB24|cit24) 2002; 26 Foury (10.1002/humu.20852-BIB10|cit10) 1992; 11 Magnusson (10.1002/humu.20852-BIB20|cit20) 2003; 289 Yakubovskaya (10.1002/humu.20852-BIB33|cit33) 2006; 281 Yakubovskaya (10.1002/humu.20852-BIB34|cit34) 2007; 26 Naviaux (10.1002/humu.20852-BIB22|cit22) 1999; 45 Chan (10.1002/humu.20852-BIB6|cit6) 2006; 15 Tashiro (10.1002/humu.20852-BIB30|cit30) 1978; 84 Stuart (10.1002/humu.20852-BIB29|cit29) 2006; 15 Baruffini (10.1002/humu.20852-BIB1|cit1) 2006; 15 Pagnamenta (10.1002/humu.20852-BIB25|cit25) 2006; 21 Graziewicz (10.1002/humu.20852-BIB13|cit13) 2006; 106 Chan (10.1002/humu.20852-BIB5|cit5) 2005; 280 Baruffini (10.1002/humu.20852-BIB2|cit2) 2007; 1772 Bodnar (10.1002/humu.20852-BIB4|cit4) 1995; 305 Van Goethem (10.1002/humu.20852-BIB31|cit31) 2001; 28 Luoma (10.1002/humu.20852-BIB19|cit19) 2005; 14 Elpeleg (10.1002/humu.20852-BIB7|cit7) 2005; 76 Wang (10.1002/humu.20852-BIB32|cit32) 1991; 60 Blake (10.1002/humu.20852-BIB3|cit3) 1999; 155 Fan (10.1002/humu.20852-BIB8|cit8) 2006; 358 Graziewicz (10.1002/humu.20852-BIB12|cit12) 2004; 11 Kapsa (10.1002/humu.20852-BIB15|cit15) 1998; 26 Naviaux (10.1002/humu.20852-BIB23|cit23) 2004; 55 Spinazzola (10.1002/humu.20852-BIB28|cit28) 2006; 38 Graziewicz (10.1002/humu.20852-BIB14|cit14) 2007; 16 Mandel (10.1002/humu.20852-BIB21|cit21) 2001; 29 Ferrari (10.1002/humu.20852-BIB9|cit9) 2005; 128 Rickwood (10.1002/humu.20852-BIB26|cit26) 1987 Gray (10.1002/humu.20852-BIB11|cit11) 1992; 267 Sarzi (10.1002/humu.20852-BIB27|cit27) 2007; 62 Lim (10.1002/humu.20852-BIB17|cit17) 1999; 274 Longley (10.1002/humu.20852-BIB18|cit18) 1998; 37 King (10.1002/humu.20852-BIB16|cit16) 1989; 246 |
| References_xml | – volume: 1772 start-page: 1225 year: 2007 end-page: 1235 article-title: Mitochondrial DNA defects in caused by functional interactions between DNA polymerase γ mutations associated with disease in human publication-title: Biochim Biophys Acta – volume: 280 start-page: 31341 year: 2005 end-page: 31346 article-title: The common A467T mutation in the human mitochondrial DNA polymerase ( ) compromises catalytic efficiency and interaction with the accessory subunit publication-title: J Biol Chem – volume: 29 start-page: 337 year: 2001 end-page: 341 article-title: The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA publication-title: Nat Genet – volume: 84 start-page: 385 year: 1978 end-page: 393 article-title: Ribonuclease H from rat liver. I. Partial purification and characterization of nuclear ribonuclease H1 publication-title: J Biochem – volume: 28 start-page: 211 year: 2001 end-page: 212 article-title: Mutation of is associated with progressive external ophthalmoplegia characterized by mtDNA deletions publication-title: Nat Genet – volume: 37 start-page: 10529 year: 1998 end-page: 10539 article-title: Characterization of the native and recombinant catalytic subunit of human DNA polymerase γ: identification of residues critical for exonuclease activity and dideoxynucleotide sensitivity publication-title: Biochemistry – volume: 305 start-page: 817 year: 1995 end-page: 822 article-title: Respiratory‐deficient human fibroblasts exhibiting defective mitochondrial DNA replication publication-title: Biochem J – volume: 11 start-page: 2717 year: 1992 end-page: 2726 article-title: Yeast mitochondrial DNA mutators with deficient proofreading exonucleolytic activity publication-title: EMBO J – volume: 155 start-page: 67 year: 1999 end-page: 70 article-title: Mitochondrial DNA depletion syndrome is expressed in amniotic fluid cell cultures publication-title: Am J Pathol – volume: 14 start-page: 1907 year: 2005 end-page: 1920 article-title: Functional defects due to spacer region mutations of human mitochondrial DNA polymerase in a family with an ataxia‐myopathy syndrome publication-title: Hum Mol Genet – volume: 15 start-page: 3473 year: 2006 end-page: 3483 article-title: Modulation of the W748S mutation in DNA polymerase γ by the E1143G polymorphism in mitochondrial disorders publication-title: Hum Mol Genet – volume: 55 start-page: 706 year: 2004 end-page: 712 article-title: mutations associated with Alpers' syndrome and mitochondrial DNA depletion publication-title: Ann Neurol – volume: 26 start-page: 4283 year: 2007 end-page: 4291 article-title: The EM structure of human DNA polymerase γ reveals a localized contact between the catalytic and accessory subunits publication-title: EMBO J – volume: 246 start-page: 500 year: 1989 end-page: 503 article-title: Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation publication-title: Science – volume: 16 start-page: 2729 year: 2007 end-page: 2739 article-title: The DNA polymerase γ Y955C disease variant associated with PEO and parkinsonism mediates the incorporation and translesion synthesis opposite 7,8‐dihydro‐8‐oxo‐2′‐deoxyguanosine publication-title: Hum Mol Genet – volume: 289 start-page: 133 year: 2003 end-page: 142 article-title: Replication of mitochondrial DNA occurs throughout the mitochondria of cultured human cells publication-title: Exp Cell Res – volume: 128 start-page: 723 year: 2005 end-page: 731 article-title: Infantile hepatocerebral syndromes associated with mutations in the mitochondrial DNA polymerase‐γA publication-title: Brain – volume: 15 start-page: 2846 year: 2006 end-page: 2855 article-title: Genetic and chemical rescue of the phenotype induced by mitochondrial DNA polymerase mutations associated with progressive external ophthalmoplegia in humans publication-title: Hum Mol Genet – volume: 21 start-page: 2467 year: 2006 end-page: 2473 article-title: Dominant inheritance of premature ovarian failure associated with mutant mitochondrial DNA polymerase gamma publication-title: Hum Reprod – volume: 267 start-page: 5835 year: 1992 end-page: 5841 article-title: Purification and identification of subunit structure of the human mitochondrial DNA polymerase publication-title: J Biol Chem – volume: 76 start-page: 1081 year: 2005 end-page: 1086 article-title: Deficiency of the ADP‐forming succinyl‐CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion publication-title: Am J Hum Genet – volume: 26 start-page: 327 year: 2002 end-page: 334 article-title: Blue Native electrophoresis to study mitochondrial and other protein complexes publication-title: Methods – volume: 274 start-page: 38197 year: 1999 end-page: 38203 article-title: The mitochondrial p55 accessory subunit of human DNA polymerase γ enhances DNA binding, promotes processive DNA synthesis, and confers ‐ethylmaleimide resistance publication-title: J Biol Chem – volume: 15 start-page: 363 year: 2006 end-page: 374 article-title: Mitochondrial and nuclear DNA defects in with mutations in DNA polymerase γ associated with progressive external ophthalmoplegia publication-title: Hum Mol Genet – volume: 60 start-page: 513 year: 1991 end-page: 552 article-title: Eukaryotic DNA polymerases publication-title: Annu Rev Biochem – volume: 358 start-page: 1229 year: 2006 end-page: 1243 article-title: A novel processive mechanism for DNA synthesis revealed by structure, modeling and mutagenesis of the accessory subunit of human mitochondrial DNA polymerase publication-title: J Mol Biol – start-page: 1 year: 1987 end-page: 16 – volume: 62 start-page: 579 year: 2007 end-page: 587 article-title: Twinkle helicase ( ) gene mutation causes mitochondrial DNA depletion publication-title: Ann Neurol – volume: 38 start-page: 570 year: 2006 end-page: 575 article-title: encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion publication-title: Nat Genet – volume: 106 start-page: 383 year: 2006 end-page: 405 article-title: DNA polymerase γ in mitochondrial DNA replication and repair publication-title: Chem Rev – volume: 11 start-page: 770 year: 2004 end-page: 776 article-title: Structure‐function defects of human mitochondrial DNA polymerase in autosomal dominant progressive external ophthalmoplegia publication-title: Nat Struct Mol Biol – volume: 26 start-page: 4365 year: 1998 end-page: 4373 article-title: mtDNA replicative potential remains constant during ageing: polymerase γ activity does not correlate with age related cytochrome oxidase activity decline in platelets publication-title: Nucleic Acids Res – volume: 45 start-page: 1725 year: 1999 end-page: 1733 article-title: Sensitive assay for mitochondrial DNA polymerase γ publication-title: Clin Chem – volume: 281 start-page: 374 year: 2006 end-page: 382 article-title: Functional human mitochondrial DNA polymerase γ forms a heterotrimer publication-title: J Biol Chem – volume: 15 start-page: 3473 year: 2006 ident: 10.1002/humu.20852-BIB6|cit6 article-title: Modulation of the W748S mutation in DNA polymerase γ by the E1143G polymorphism in mitochondrial disorders publication-title: Hum Mol Genet doi: 10.1093/hmg/ddl424 – volume: 358 start-page: 1229 year: 2006 ident: 10.1002/humu.20852-BIB8|cit8 article-title: A novel processive mechanism for DNA synthesis revealed by structure, modeling and mutagenesis of the accessory subunit of human mitochondrial DNA polymerase publication-title: J Mol Biol doi: 10.1016/j.jmb.2006.02.073 – volume: 26 start-page: 327 year: 2002 ident: 10.1002/humu.20852-BIB24|cit24 article-title: Blue Native electrophoresis to study mitochondrial and other protein complexes publication-title: Methods doi: 10.1016/S1046-2023(02)00038-5 – volume: 280 start-page: 31341 year: 2005 ident: 10.1002/humu.20852-BIB5|cit5 article-title: The common A467T mutation in the human mitochondrial DNA polymerase (POLG) compromises catalytic efficiency and interaction with the accessory subunit publication-title: J Biol Chem doi: 10.1074/jbc.M506762200 – volume: 37 start-page: 10529 year: 1998 ident: 10.1002/humu.20852-BIB18|cit18 article-title: Characterization of the native and recombinant catalytic subunit of human DNA polymerase γ: identification of residues critical for exonuclease activity and dideoxynucleotide sensitivity publication-title: Biochemistry doi: 10.1021/bi980772w – start-page: 1 volume-title: Mitochondria: a practical approach year: 1987 ident: 10.1002/humu.20852-BIB26|cit26 – volume: 16 start-page: 2729 year: 2007 ident: 10.1002/humu.20852-BIB14|cit14 article-title: The DNA polymerase γ Y955C disease variant associated with PEO and parkinsonism mediates the incorporation and translesion synthesis opposite 7,8-dihydro-8-oxo-2′-deoxyguanosine publication-title: Hum Mol Genet doi: 10.1093/hmg/ddm227 – volume: 84 start-page: 385 year: 1978 ident: 10.1002/humu.20852-BIB30|cit30 article-title: Ribonuclease H from rat liver. I. Partial purification and characterization of nuclear ribonuclease H1 publication-title: J Biochem doi: 10.1093/oxfordjournals.jbchem.a132139 – volume: 1772 start-page: 1225 year: 2007 ident: 10.1002/humu.20852-BIB2|cit2 article-title: Mitochondrial DNA defects in Saccharomyces cerevisiae caused by functional interactions between DNA polymerase γ mutations associated with disease in human publication-title: Biochim Biophys Acta doi: 10.1016/j.bbadis.2007.10.002 – volume: 76 start-page: 1081 year: 2005 ident: 10.1002/humu.20852-BIB7|cit7 article-title: Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion publication-title: Am J Hum Genet doi: 10.1086/430843 – volume: 281 start-page: 374 year: 2006 ident: 10.1002/humu.20852-BIB33|cit33 article-title: Functional human mitochondrial DNA polymerase γ forms a heterotrimer publication-title: J Biol Chem doi: 10.1074/jbc.M509730200 – volume: 128 start-page: 723 year: 2005 ident: 10.1002/humu.20852-BIB9|cit9 article-title: Infantile hepatocerebral syndromes associated with mutations in the mitochondrial DNA polymerase-γA publication-title: Brain doi: 10.1093/brain/awh410 – volume: 11 start-page: 2717 year: 1992 ident: 10.1002/humu.20852-BIB10|cit10 article-title: Yeast mitochondrial DNA mutators with deficient proofreading exonucleolytic activity publication-title: EMBO J doi: 10.1002/j.1460-2075.1992.tb05337.x – volume: 11 start-page: 770 year: 2004 ident: 10.1002/humu.20852-BIB12|cit12 article-title: Structure-function defects of human mitochondrial DNA polymerase in autosomal dominant progressive external ophthalmoplegia publication-title: Nat Struct Mol Biol doi: 10.1038/nsmb805 – volume: 106 start-page: 383 year: 2006 ident: 10.1002/humu.20852-BIB13|cit13 article-title: DNA polymerase γ in mitochondrial DNA replication and repair publication-title: Chem Rev doi: 10.1021/cr040463d – volume: 246 start-page: 500 year: 1989 ident: 10.1002/humu.20852-BIB16|cit16 article-title: Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation publication-title: Science doi: 10.1126/science.2814477 – volume: 289 start-page: 133 year: 2003 ident: 10.1002/humu.20852-BIB20|cit20 article-title: Replication of mitochondrial DNA occurs throughout the mitochondria of cultured human cells publication-title: Exp Cell Res doi: 10.1016/S0014-4827(03)00249-0 – volume: 26 start-page: 4365 year: 1998 ident: 10.1002/humu.20852-BIB15|cit15 article-title: mtDNA replicative potential remains constant during ageing: polymerase γ activity does not correlate with age related cytochrome oxidase activity decline in platelets publication-title: Nucleic Acids Res doi: 10.1093/nar/26.19.4365 – volume: 29 start-page: 337 year: 2001 ident: 10.1002/humu.20852-BIB21|cit21 article-title: The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA publication-title: Nat Genet doi: 10.1038/ng746 – volume: 14 start-page: 1907 year: 2005 ident: 10.1002/humu.20852-BIB19|cit19 article-title: Functional defects due to spacer region mutations of human mitochondrial DNA polymerase in a family with an ataxia-myopathy syndrome publication-title: Hum Mol Genet doi: 10.1093/hmg/ddi196 – volume: 274 start-page: 38197 year: 1999 ident: 10.1002/humu.20852-BIB17|cit17 article-title: The mitochondrial p55 accessory subunit of human DNA polymerase γ enhances DNA binding, promotes processive DNA synthesis, and confers N-ethylmaleimide resistance publication-title: J Biol Chem doi: 10.1074/jbc.274.53.38197 – volume: 55 start-page: 706 year: 2004 ident: 10.1002/humu.20852-BIB23|cit23 article-title: POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion publication-title: Ann Neurol doi: 10.1002/ana.20079 – volume: 45 start-page: 1725 year: 1999 ident: 10.1002/humu.20852-BIB22|cit22 article-title: Sensitive assay for mitochondrial DNA polymerase γ publication-title: Clin Chem doi: 10.1093/clinchem/45.10.1725 – volume: 28 start-page: 211 year: 2001 ident: 10.1002/humu.20852-BIB31|cit31 article-title: Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions publication-title: Nat Genet doi: 10.1038/90034 – volume: 305 start-page: 817 year: 1995 ident: 10.1002/humu.20852-BIB4|cit4 article-title: Respiratory-deficient human fibroblasts exhibiting defective mitochondrial DNA replication publication-title: Biochem J doi: 10.1042/bj3050817 – volume: 155 start-page: 67 year: 1999 ident: 10.1002/humu.20852-BIB3|cit3 article-title: Mitochondrial DNA depletion syndrome is expressed in amniotic fluid cell cultures publication-title: Am J Pathol doi: 10.1016/S0002-9440(10)65100-0 – volume: 21 start-page: 2467 year: 2006 ident: 10.1002/humu.20852-BIB25|cit25 article-title: Dominant inheritance of premature ovarian failure associated with mutant mitochondrial DNA polymerase gamma publication-title: Hum Reprod doi: 10.1093/humrep/del076 – volume: 60 start-page: 513 year: 1991 ident: 10.1002/humu.20852-BIB32|cit32 article-title: Eukaryotic DNA polymerases publication-title: Annu Rev Biochem doi: 10.1146/annurev.bi.60.070191.002501 – volume: 62 start-page: 579 year: 2007 ident: 10.1002/humu.20852-BIB27|cit27 article-title: Twinkle helicase (PEO1) gene mutation causes mitochondrial DNA depletion publication-title: Ann Neurol doi: 10.1002/ana.21207 – volume: 38 start-page: 570 year: 2006 ident: 10.1002/humu.20852-BIB28|cit28 article-title: MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion publication-title: Nat Genet doi: 10.1038/ng1765 – volume: 15 start-page: 2846 year: 2006 ident: 10.1002/humu.20852-BIB1|cit1 article-title: Genetic and chemical rescue of the Saccharomyces cerevisiae phenotype induced by mitochondrial DNA polymerase mutations associated with progressive external ophthalmoplegia in humans publication-title: Hum Mol Genet doi: 10.1093/hmg/ddl219 – volume: 267 start-page: 5835 year: 1992 ident: 10.1002/humu.20852-BIB11|cit11 article-title: Purification and identification of subunit structure of the human mitochondrial DNA polymerase publication-title: J Biol Chem doi: 10.1016/S0021-9258(18)42629-4 – volume: 15 start-page: 363 year: 2006 ident: 10.1002/humu.20852-BIB29|cit29 article-title: Mitochondrial and nuclear DNA defects in Saccharomyces cerevisiae with mutations in DNA polymerase γ associated with progressive external ophthalmoplegia publication-title: Hum Mol Genet doi: 10.1093/hmg/ddi454 – volume: 26 start-page: 4283 year: 2007 ident: 10.1002/humu.20852-BIB34|cit34 article-title: The EM structure of human DNA polymerase γ reveals a localized contact between the catalytic and accessory subunits publication-title: EMBO J doi: 10.1038/sj.emboj.7601843 |
| SSID | ssj0008553 |
| Score | 2.1387322 |
| Snippet | We studied six unrelated children with depletion of mitochondrial DNA (mtDNA). They presented with Leigh syndrome, infantile hepatocerebral mtDNA depletion... |
| SourceID | proquest pubmed crossref wiley fao |
| SourceType | Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 248 |
| SubjectTerms | Adolescent Alpers‐Huttenlocher syndrome Cells, Cultured DNA Mutational Analysis DNA Polymerase gamma DNA polymerase γ DNA, Mitochondrial - genetics DNA-Directed DNA Polymerase - genetics DNA-Directed DNA Polymerase - metabolism Female Fibroblasts - enzymology Holoenzymes - metabolism Humans Immunoblotting Infant Infant, Newborn Leigh syndrome Male mitochondrial DNA mitochondrial DNA depletion syndrome mtDNA Mutation - genetics POLG |
| Title | Analysis of mutant DNA polymerase γ in patients with mitochondrial DNA depletion |
| URI | https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fhumu.20852 https://www.ncbi.nlm.nih.gov/pubmed/18828154 https://www.proquest.com/docview/1776650325 https://www.proquest.com/docview/20559764 https://www.proquest.com/docview/66880325 |
| Volume | 30 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| journalDatabaseRights | – providerCode: PRVWIB databaseName: Wiley Online Library - Core collection (SURFmarket) issn: 1059-7794 databaseCode: DR2 dateStart: 19960101 customDbUrl: isFulltext: true eissn: 1098-1004 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0008553 providerName: Wiley-Blackwell |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwEB6VSiAuBcqjoTyM4AJSths7cWyJSwVUK6StxCNSL8iyHYdW7SYrdnMof6v_g9_E2El2VdQiwS2HseXYM-NvPPY3AK84M5IJU8ZpSV2c5rSKtRUs1iz38FUaJ_3b4ekhnxTpx6PsaAPeDm9hOn6I1YGbt4zgr72Ba7PYW5OGHrezduQrTHoHnLAs5Gg_r7mjRJZ1t-sziRBSpituUrq3bnppN7pR6eYqoHkZt4aN5-AOfBuG3N03OR21SzOyP_9gc_zff7oLWz0iJfudCt2DDVdvw82uRuX5Ntya9tn3-_BpYDAhTUVmra8_TN4f7pN5c3buz7YWjvy6ICc16claF8Sf8pIZOg10snXpdT00KN3cc3439QMoDj58fTeJ-5IMsfU7PbqjDMNpXVpmrBgbYcfCVlKWVlacOkQH0rHSJFWVUZ4j0kqopUlV6kpLy3Ij2EPYrJva7QDRLtepYJaPNQpSKRiCT2oENYY5SU0Er4elUbbnK_dlM85Ux7RMlZ8tFWYrgpcr2XnH0nGl1A6usNLf0X2q4gv1SVtEcwlGuBG8GJZdoX35pImuXdMuVJLnHFEso1kEz6-RoWMfl_H0egnO0U-GPh51OrUeJoY4AnFsBG-CZvxl_GpSTIvw9fhfhHfhdpcC83dwnsDm8kfrniKSWppnwWJ-A70iF6g |
| linkProvider | Wiley-Blackwell |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwELagCMqFR3k0vGoEF5Cy3dh52MeKUi3QXQlopN4s23Eoopus2M2h_C3-B7-JGTu7q6IWCW45jCMnnhl_4xl_Q8jLnBvJhanitGIuTgtWx9oKHmteIHyVxkm8Ozye5KMyfX-cHfe1OXgXJvBDrA7c0DK8v0YDxwPp3TVr6Ek37QbYYhI88DVM0KFd7n9as0eJLAv19ZkEECnTFTsp212PPbcfXa11exHUPI9c_dZzcDv0V517xkKsOPk26BZmYH_8wef43191h9zqQSndC1p0l1xxzRa5HtpUnm2RG-M-AX-PfFySmNC2ptMOWxDT_ckenbWnZ3i8NXf010_6taE9X-uc4kEvnYLfAD_bVKjufkDlZkj73Tb3SXnw9ujNKO67MsQWN3vwSBlE1Lqy3FgxNMIOha2lrKysc-YAIEjHK5PUdcbyAsBWwixL6krXWlpeGMEfkI2mbdw2odoVOhXc5kMNgkwKDviTGcGM4U4yE5FXy7VRtqcsx84ZpyqQLTOFf0v5vxWRFyvZWSDquFBqG5ZY6S_gQVX5mWHeFgBdAkFuRJ4v112BiWHeRDeu7eYqKYocgCxnWUR2LpFhQwzN8vRyiTwHV-nf8TAo1XqaEOUIgLIRee1V4y_zV6NyXPqnR_8ivEM2R0fjQ3X4bvLhMbkZMmJYkvOEbCy-d-4pAKuFeebN5zcrHhvE |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwEB6VIiouPMqj4VUjuICU7cZOHFviUlFWy2NXvCL1gizbcVpEN1mxm0P5W_wPfhPjPHZV1CLBLYex5dgz42889jcATzkzkgmTh3FOXRintAi1FSzULPXwVRon_dvhyZSPs_jNYXK4AS_6tzAtP8TqwM1bRuOvvYHP82JvTRp6XM_qga8wiQ74cswxvPKQ6OOaPEokSXu9PpGIIWW8Iiele-u2Z7ajS4WuzkOaZ4Frs_OMrsOXfszthZNvg3ppBvbHH3SO__tTN-BaB0nJfqtDN2HDldtwpS1SeboNW5Mu_X4LPvQUJqQqyKz2BYjJwXSfzKuTU3-4tXDk10_ytSQdW-uC-GNeMkOvgV62zL2yNw1yN_ek31V5G7LRq88vx2FXkyG0fqtHf5RgPK1zy4wVQyPsUNhCytzKglOH8EA6lpuoKBLKU4RaEbU0KnJdaGlZagS7A5tlVbodINqlOhbM8qFGQSoFQ_RJjaDGMCepCeBZvzTKdoTlvm7GiWqplqnys6Wa2QrgyUp23tJ0nCu1gyus9BH6T5V9oj5ri3AuwhA3gMf9sis0MJ810aWr6oWK0pQjjGU0CWD3Ahk69IEZjy-W4BwdZdPH3Van1sPEGEcgkA3geaMZfxm_GmeTrPm69y_Cu7D1_mCk3r2evr0PV9t0mL-P8wA2l99r9xBR1dI8aoznN8FuGnM |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Analysis+of+mutant+DNA+polymerase+%CE%B3+in+patients+with+mitochondrial+DNA+depletion&rft.jtitle=Human+mutation&rft.au=Taanman%2C+Jan%E2%80%90Willem&rft.au=Rahman%2C+Shamima&rft.au=Pagnamenta%2C+Alistair+T.&rft.au=Morris%2C+Andrew+A.M.&rft.date=2009-02-01&rft.pub=Wiley+Subscription+Services%2C+Inc.%2C+A+Wiley+Company&rft.issn=1059-7794&rft.eissn=1098-1004&rft.volume=30&rft.issue=2&rft.spage=248&rft.epage=254&rft_id=info:doi/10.1002%2Fhumu.20852&rft.externalDBID=10.1002%252Fhumu.20852&rft.externalDocID=HUMU20852 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1059-7794&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1059-7794&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1059-7794&client=summon |