1. Academic Validation
  2. Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells

Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells

  • Mol Cell. 2010 Mar 12;37(5):714-27. doi: 10.1016/j.molcel.2010.02.009.
Tomoo Ogi 1 Siripan Limsirichaikul René M Overmeer Marcel Volker Katsuya Takenaka Ross Cloney Yuka Nakazawa Atsuko Niimi Yoshio Miki Nicolaas G Jaspers Leon H F Mullenders Shunichi Yamashita Maria I Fousteri Alan R Lehmann
Affiliations

Affiliation

  • 1 Department of Molecular Medicine, Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki 852-8523, Japan. togi@nagasaki-u.ac.jp
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.

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