MOLECULAR-CELL-D-09-00592-1.pdf (1.87 MB)
Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells
journal contributionposted on 2023-06-07, 15:18 authored by Tomoo Ogi, Siripan Limsirichaikul, René M Overmeer, Marcel Volker, Katsuya Takenaka, Ross Cloney, Yuka Nakazawa, Atsuko Niimi, Yoshio Miki, Nicolaas G Japers, Leon H F Mullenders., Shunichi Yamashita, Maria I Fousteri, Alan LehmannAlan Lehmann
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? and pold, and both polymerases can be recovered in the same repair complexes. Pol? is recruited to repair sites by ubiquitinated PCNA and XRCC1 and pold 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?, recruitment of which is dependent on the alternative clamp loader CTF18-RFC.
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