期刊
DNA REPAIR
卷 9, 期 2, 页码 109-119出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.dnarep.2009.11.002
关键词
UV damage endonuclease; Long patch base excision repair; DNA polymerase beta; Flap endonuclease 1; Thymine dimer
资金
- NIH [1 R01 AG24364-01, 1 P20 CA132385-01, CA40463]
- National Institute of Environmental Health Sciences [ZO1-ES050158, Z01-ES050159]
- American Cancer Society [RSG-05-246-01-GMC]
- Ministry of Education, Science, Sports and Culture of Japan
We examined a role for DNA polymerase beta (Pol beta) in mammalian long patch base excision repair (LP BER). Although a role for Pol beta is well known in single-nucleotide BER, information on this enzyme in the context of LP BER has been limited. To examine the question of Pol beta involvement in LP BER, we made use of nucleotide excision repair-deficient human XPA cells expressing UVDE (XPA-UVDE), which introduces a nick directly 5' to the cyclobutane pyrimidine dimer or 6-4 photoproduct, leaving ends with 3'-OH and 5'-phosphorylated UV lesion. We observed recruitment of GFP-fused Pol beta to focal sites of nuclear UV irradiation, consistent with a role of Pol beta in repair of UV-induced photoproducts adjacent to a strand break. This was the first evidence of Pol recruitment in LP BER in vivo. In cell extract, a 5'-blocked oligodeoxynucleotide substrate containing a nicked 5'-cyclobutane pyrimidine dimer was repaired by Pol beta-dependent LP BER. We also demonstrated Pol beta involvement in LP BER by making use of mouse cells that are double null for XPA and Pol beta. These results were extended by experiments with oligodeoxynucleotide substrates and purified human Pol beta. Published by Elsevier B.V.
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