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

Bienko, Marzena, Green, Catherine M, Crosetto, Nicola, Rudolf, Fabian, Zapart, Grzegorz, Coull, Barry, Kannouche, Patricia, Wider, Gerhard, Peter, Matthias, Lehmann, Alan R, Hofmann, Kay, Dikic, Ivan and Unset (2005) Ubiquitin-Binding Domains in Y-Family Polymerases Regulate Translesion Synthesis. Science, 310 (5575). pp. 1821-1824. ISSN 0036-8075

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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 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.

Item Type: Article
Additional Information: 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.
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: EPrints Services
Date Deposited: 06 Feb 2012 19:27
Last Modified: 30 Mar 2012 09:13
URI: http://sro.sussex.ac.uk/id/eprint/20685
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