Three DNA Polymerases, Recruited by Different Mechanisms, Carry Out NER Repair Synthesis in Human Cells

Ogi, Tomoo, Limsirichaikul, Siripan, Overmeer, René M, Volker, Marcel, Takenaka, Katsuya, Cloney, Ross, Nakazawa, Yuka, Niimi, Atsuko, Miki, Yoshio, Jaspers, Nicolaas G, Mullenders, Leon H F, Yamashita, Shunichi, Fousteri, Maria I and Lehmann, Alan R (2010) Three DNA Polymerases, Recruited by Different Mechanisms, Carry Out NER Repair Synthesis in Human Cells. Molecular Cell, 37 (5). pp. 714-727. ISSN 1097-2765

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Abstract

Nucleotide excision repair (NER) is the most versatile DNA repair system that deals with the major UV photoproducts in DNA, as well as many other DNA adducts. The early steps of NER are well understood, whereas the later steps of repair synthesis and ligation are not. In particular, which polymerases are definitely involved in repair synthesis and how they are recruited to the damaged sites has not yet been established. We report that, in human fibroblasts, approximately half of the repair synthesis requires both pol kappa and pol delta, and both polymerases can be recovered in the same repair complexes. Pol kappa is recruited to repair sites by ubiquitinated PCNA and XRCC1 and pol delta by the classical replication factor complex RFC1-RFC, together with a polymerase accessory factor, p66, and unmodified PCNA. The remaining repair synthesis is dependent on pol epsilon, recruitment of which is dependent on the alternative clamp loader CTF18-RFC.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science
Depositing User: Marcel Volker
Date Deposited: 06 Feb 2012 19:32
Last Modified: 15 Oct 2012 13:01
URI: http://sro.sussex.ac.uk/id/eprint/21116
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