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Regulation of Translesion Synthesis DNA Polymerase ? by Monoubiquitination

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posted on 2023-06-07, 19:57 authored by Marzena Bienko, Catherine M Green, Simone Sabbioneda, Nicola Crosetto, Ivan Matic, Richard G Hibbert, Tihana Begovic, Atsuko Niimi, Alan LehmannAlan Lehmann, Ivan Dikic
DNA polymerase eta is a Y family polymerase involved in translesion synthesis (TLS). Its action is initiated by simultaneous interaction between the PIP box in pol eta and PCNA and between the UBZ in pol eta and monoubiquitin attached to PCNA. Whereas monoubiquitination of PCNA is required for its interaction with pol eta during TLS, we now show that monoubiquitination of pol eta inhibits this interaction, preventing its functions in undamaged cells. Identification of monoubiquitination sites within pol eta nuclear localization signal (NLS) led to the discovery that pol eta NLS directly contacts PCNA, forming an extended pol eta-PCNA interaction surface. We name this the PCNA-interacting region (PIR) and show that its monoubiquitination is downregulated by various DNA-damaging agents. We propose that this mechanism ensures optimal availability of nonubiquitinated, TLS-competent pol eta after DNA damage. Our work shows how monoubiquitination can either positively or negatively regulate the assembly of a protein complex, depending on which substrates are targeted by ubiquitin.

History

Publication status

  • Published

File Version

  • Accepted version

Journal

Molecular Cell

ISSN

1097-2765

Publisher

Elsevier

Issue

3

Volume

37

Page range

396-407

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

First Open Access (FOA) Date

2012-03-29

First Compliant Deposit (FCD) Date

2012-03-29

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