A novel function of DNA polymerase ζ regulated by PCNA
- 7 September 2006
- journal article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 25 (18), 4316-4325
- https://doi.org/10.1038/sj.emboj.7601320
Abstract
DNA polymerase ζ (Polζ) participates in translesion DNA synthesis and is involved in the generation of the majority of mutations induced by DNA damage. The mechanisms that license access of Polζ to the primer terminus and regulate the extent of its participation in genome replication are poorly understood. The Polζ‐dependent damage‐induced mutagenesis requires monoubiquitination of proliferating cell nuclear antigen (PCNA) that is triggered by exposure to mutagens. We show that Polζ contributes to DNA replication and causes mutagenesis not only in response to DNA damage but also in response to malfunction of normal replicative machinery due to mutations in replication genes. These replication defects lead to ubiquitination of PCNA even in the absence of DNA damage. Unlike damage‐induced mutagenesis, the Polζ‐dependent spontaneous mutagenesis in replication mutants is reduced in strains defective in both ubiquitination and sumoylation of Lys164 of PCNA. Additionally, studies of a PCNA mutant defective for functional interactions with Polζ, but not for monoubiquitination by the Rad6/Rad18 complex demonstrate a role for PCNA in regulating the mutagenic activity of Polζ separate from its modification at Lys164.Keywords
This publication has 61 references indexed in Scilit:
- The fidelity of DNA synthesis by yeast DNA polymerase zeta alone and with accessory proteinsNucleic Acids Research, 2006
- The Saccharomyces cerevisiae rev6-1 Mutation, Which Inhibits Both the Lesion Bypass and the Recombination Mode of DNA Damage Tolerance, Is an Allele of POL30, Encoding Proliferating Cell Nuclear AntigenGenetics, 2006
- Controlling the subcellular localization of DNA polymerases ι and η via interactions with ubiquitinThe EMBO Journal, 2006
- SUMO-modified PCNA recruits Srs2 to prevent recombination during S phaseNature, 2005
- The Relative Roles in Vivo of Saccharomyces cerevisiae Pol η, Pol ζ, Rev1 Protein and Pol32 in the Bypass and Mutation Induction of an Abasic Site, T-T (6-4) Photoadduct and T-T cis-syn Cyclobutane DimerGenetics, 2005
- Benzo[a]pyrene diol epoxide–deoxyguanosine adducts are accurately bypassed by yeast DNA polymerase ζ in vitroMutation Research, 2002
- RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMONature, 2002
- Interaction with PCNA Is Essential for Yeast DNA Polymerase η FunctionMolecular Cell, 2001
- Mutator effects of overproducing DNA polymerase η (Rad30) and its catalytically inactive variant in yeastMutation Research, 2001
- New heterologous modules for classical or PCR‐based gene disruptions in Saccharomyces cerevisiaeYeast, 1994