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

Tomoo Ogi, 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

Research output: Contribution to journalArticlepeer-review

238 Citations (Scopus)

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 polκ and polδ, and both polymerases can be recovered in the same repair complexes. Polκ is recruited to repair sites by ubiquitinated PCNA and XRCC1 and polδ 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 polε, recruitment of which is dependent on the alternative clamp loader CTF18-RFC.

Original languageEnglish
Pages (from-to)714-727
Number of pages14
JournalMolecular Cell
Volume37
Issue number5
DOIs
Publication statusPublished - 12-03-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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