First Author | Shachar S | Year | 2009 |
Journal | EMBO J | Volume | 28 |
Issue | 4 | Pages | 383-93 |
PubMed ID | 19153606 | Mgi Jnum | J:145851 |
Mgi Id | MGI:3836199 | Doi | 10.1038/emboj.2008.281 |
Citation | Shachar S, et al. (2009) Two-polymerase mechanisms dictate error-free and error-prone translesion DNA synthesis in mammals. EMBO J 28(4):383-93 |
abstractText | 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 zeta (pol zeta), 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 pol zeta dictate error-prone or error-free TLS across the same lesion. These results highlight the central role of pol zeta 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. |