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Distinct requirements for budding yeast Rev1 and Polη in translesion DNA synthesis across different types of DNA damage

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Abstract

Certain replication-blocking lesions can escape DNA repair and must be bypassed to prevent fork collapse and cell death. Budding yeast DNA-damage tolerance consists of translesion DNA synthesis (TLS) and template switch. TLS utilizes specialized DNA polymerases to insert nucleotides opposite the damage site, followed by extension, allowing continual replication in the presence of lesions on the template DNA. Meanwhile, Rev1 is additionally required for the subsequent extension step of TLS regardless of the initial insertion polymerase utilized. Here we assess relative contributions of two Y-family TLS polymerases, Rev1 and Polη, in bypassing lesions induced by various types of DNA-damaging agents. Our experimental results collectively indicate that yeast cells preferentially utilize relatively error-free TLS polymerase(s) to bypass given lesions, and that the mutagenic TLS polymerase may serve as a backup. Interestingly, if Polη is unable to serve as a TLS polymerase under certain circumstances, it may be counter-active. The cooperation among TLS polymerases may strike a balance between survival and stress-induced mutagenesis. These observations indicate that specialized Y-family DNA polymerases have evolved to deal with different types of environmental genotoxic stresses.

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Acknowledgements

The authors wish to thank Michelle Hanna for proofreading the manuscript, the Xiao laboratory members for helpful discussion and the anonymous reviewers for constructive comments. This work was supported by the National Natural Science Foundation of China operating grant 31670068 and Natural Sciences and Engineering Research Council of Canada Discovery Grants RGPIN-2019-05604 to WX.

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Correspondence to Wei Xiao.

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Communicated by M. Kupiec.

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Wang, Z., Xiao, W. Distinct requirements for budding yeast Rev1 and Polη in translesion DNA synthesis across different types of DNA damage. Curr Genet 66, 1019–1028 (2020). https://doi.org/10.1007/s00294-020-01092-w

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