TY - JOUR
T1 - Three DNA Polymerases, Recruited by Different Mechanisms, Carry Out NER Repair Synthesis in Human Cells
AU - Ogi, Tomoo
AU - Limsirichaikul, Siripan
AU - Overmeer, René M.
AU - Volker, Marcel
AU - Takenaka, Katsuya
AU - Cloney, Ross
AU - Nakazawa, Yuka
AU - Niimi, Atsuko
AU - Miki, Yoshio
AU - Jaspers, Nicolaas G.
AU - Mullenders, Leon H.F.
AU - Yamashita, Shunichi
AU - Fousteri, Maria I.
AU - Lehmann, Alan R.
N1 - Funding Information:
This work was supported by Special Coordination Funds for Promoting Science and Technology from Japan Science and Technology Agency (JST), a Grant in aid for Scientific Research KAKENHI (20810021) from Japan Society for the Promotion of Science, a cancer research grant from the YASUDA Medical Foundation, a research grant from Uehara Memorial Foundation, a medical research grant from Takeda Science Foundation, a Grant in aid for Honeybee Research from Yamada Apiculture Center Inc., a Grant in aid for Seeds Innovation (Type-A) from JST, and a Butterfield Medical Award from the Great Britain Sasakawa Foundation to T.O.; a Global COE Program from the Ministry of Education, Culture, Sports, Sciences and Technology of Japan to T.O., S.L., Y.N., and S.Y.; a KAKENHI to K.T. and Y.M.; a Medical Research Council programme grant to A.R.L.; and an EC-RTN and integrated project to A.R.L. and L.M. We are grateful to Y. Gushiken for anti-polκ antibody purification. The anti-polϵ antibody, 3A3.2, is a kind gift from S. Linn (University of California, Berkeley).
PY - 2010/3/12
Y1 - 2010/3/12
N2 - 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.
AB - 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.
KW - DNA
UR - http://www.scopus.com/inward/record.url?scp=77649242633&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77649242633&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2010.02.009
DO - 10.1016/j.molcel.2010.02.009
M3 - Article
C2 - 20227374
AN - SCOPUS:77649242633
SN - 1097-2765
VL - 37
SP - 714
EP - 727
JO - Molecular Cell
JF - Molecular Cell
IS - 5
ER -