Two-polymerase mechanisms dictate error-free and error-prone translesion DNA synthesis in mammals

DNA replication across blocking lesions occurs by translesion DNA synthesis (TLS), involving a multitude of mutagenic DNA polymerases that operate to protect the mammalian genome. Using a quantitative TLS assay, we identified three main classes of TLS in human cells: two rapid and error‐free, and th...

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Vydáno v:	The EMBO journal Ročník 28; číslo 4; s. 383 - 393
Hlavní autoři:	Shachar, Sigal, Ziv, Omer, Avkin, Sharon, Adar, Sheera, Wittschieben, John, Reißner, Thomas, Chaney, Stephen, Friedberg, Errol C, Wang, Zhigang, Carell, Thomas, Geacintov, Nicholas, Livneh, Zvi
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Chichester, UK John Wiley & Sons, Ltd 18.02.2009 Nature Publishing Group UK Springer Nature B.V Nature Publishing Group
Témata:	Animals carcinogenesis Catalysis Cell Line, Tumor Cellular biology Deoxyribonucleic acid Dimerization DNA DNA - chemistry DNA - metabolism DNA Damage DNA polymerase DNA repair DNA Replication DNA-Directed DNA Polymerase - chemistry DNA-Directed DNA Polymerase - metabolism Epistasis, Genetic Genomics Humans Kinetics lesion bypass Lesions Mammals Mice Molecular biology Mutagenesis Pyrimidine Dimers - chemistry RNA, Small Interfering - metabolism Xeroderma Pigmentosum Group A Protein - metabolism carcinogenesis DNA repair mutagenesis DNA damage lesion bypass
ISSN:	0261-4189, 1460-2075, 1460-2075
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Popis
Shrnutí:	DNA replication across blocking lesions occurs by translesion DNA synthesis (TLS), involving a multitude of mutagenic DNA polymerases that operate to protect the mammalian genome. Using a quantitative TLS assay, we identified three main classes of TLS in human cells: two rapid and error‐free, and the third slow and error‐prone. A single gene, REV3L , encoding the catalytic subunit of DNA polymerase ζ (polζ), was found to have a pivotal role in TLS, being involved in TLS across all lesions examined, except for a TT cyclobutane dimer. Genetic epistasis siRNA analysis indicated that discrete two‐polymerase combinations with polζ dictate error‐prone or error‐free TLS across the same lesion. These results highlight the central role of polζ in both error‐prone and error‐free TLS in mammalian cells, and show that bypass of a single lesion may involve at least three different DNA polymerases, operating in different two‐polymerase combinations.
Bibliografie:	ArticleID:EMBJ2008281 istex:B964CBF19EFB01776736441F4889B17FF5998663 ark:/67375/WNG-5STT2SMS-K Supplementary Information ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0261-4189 1460-2075 1460-2075
DOI:	10.1038/emboj.2008.281