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Bertoletti-Sabbioneda NAR 2017.pdf (5.37 MB)

Phosphorylation regulates human pol? stability and damage bypass throughout the cell cycle

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posted on 2023-06-09, 08:15 authored by Federica Bertoletti, Valentina Cea, Chih-Chao Liang, Taiba Lanati, Antonio Maffia, Mario D M Avarello, Lina Cipolla, Alan LehmannAlan Lehmann, Martin A Cohn, Simone Sabbioneda
DNA translesion synthesis (TLS) is a crucial damage tolerance pathway that oversees the completion of DNA replication in the presence of DNA damage. TLS polymerases are capable of bypassing a distorted template but they are generally considered inaccurate and they need to be tightly regulated. We have previously shown that pol? is phosphorylated on Serine 601 after DNA damage and we have demonstrated that this modification is important for efficient damage bypass. Here we report that pol? is also phosphorylated by CDK2, in the absence of damage, in a cell cycle-dependent manner and we identify serine 687 as an important residue targeted by the kinase. We discover that phosphorylation on serine 687 regulates the stability of the polymerase during the cell cycle, allowing it to accumulate in late S and G2 when productive TLS is critical for cell survival. Furthermore, we show that alongside the phosphorylation of S601, the phosphorylation of S687 and S510, S512 and/or S514 are important for damage bypass and cell survival after UV irradiation. Taken together our results provide new insights into how cells can, at different times, modulate DNA TLS for improved cell survival.

History

Publication status

  • Published

File Version

  • Published version

Journal

Nucleic Acids Research

ISSN

1362-4962

Publisher

Oxford Journals

Issue

16

Volume

45

Page range

9441-9454

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Research groups affiliated with

  • Genome Damage and Stability Centre Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2017-10-11

First Open Access (FOA) Date

2017-10-11

First Compliant Deposit (FCD) Date

2017-10-11

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