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

Authors :
Patricia Kannouche
Alan R. Lehmann
Ivan Dikic
Gerhard Wider
Grzegorz Zapart
Marzena Bienko
Nicola Crosetto
Kay Hofmann
Fabian Rudolf
Catherine M. Green
Matthias Peter
Barry Coull
Source :
Science. 310:1821-1824
Publication Year :
2005
Publisher :
American Association for the Advancement of Science (AAAS), 2005.

Abstract

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 polη and polι to ubiquitin, their accumulation in replication factories, and their interaction with monoubiquitinated PCNA. Moreover, the UBZ domain of polη 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.

Details

ISSN :
10959203 and 00368075
Volume :
310
Database :
OpenAIRE
Journal :
Science
Accession number :
edsair.doi.dedup.....2363c71f50a597c94225447790a6fdb2
Full Text :
https://doi.org/10.1126/science.1120615