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Ubiquitin-Binding Domains in Y-Family Polymerases Regulate Translesion Synthesis

journal contribution
posted on 2023-06-07, 22:58 authored by Marzena Bienko, Catherine M Green, Nicola Crosetto, Fabian Rudolf, Grzegorz Zapart, Barry Coull, Patricia Kannouche, Gerhard Wider, Matthias Peter, Alan LehmannAlan Lehmann, Kay Hofmann, Ivan Dikic
Translesion synthesis (TLS) is the major pathway by which mammalian cells replicate across DNA lesions. Upon DNA damage, ubiquitination of proliferating cell nuclear antigen (PCNA) induces bypass of the lesion by directing the replication machinery into the TLS pathway. Yet, how this modification is recognized and interpreted in the cell remains unclear. Here we describe the identification of two ubiquitin (Ub)¿binding domains (UBM and UBZ), which are evolutionarily conserved in all Y-family TLS polymerases (pols). These domains are required for binding of pol¿ and pol¿ to ubiquitin, their accumulation in replication factories, and their interaction with monoubiquitinated PCNA. Moreover, the UBZ domain of pol¿ is essential to efficiently restore a normal response to ultraviolet irradiation in xeroderma pigmentosum variant (XP-V) fibroblasts. Our results indicate that Ub-binding domains of Y-family polymerases play crucial regulatory roles in TLS.

History

Publication status

  • Published

Journal

Science

ISSN

0036-8075

Publisher

American Association for the Advancement of Science

Issue

5575

Volume

310

Page range

1821-1824

Pages

4.0

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Notes

Significant part done in my lab. I had major intellectual input into this work, as our collaborators were not DNA repair experts, so I made many suggestions for critical experiments and the paper was written jointly. It described novel ubiquitin-binding domains in all members of the Y-family of DNA polymerases.

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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