Processing of UV damage in vitro by FEN-1 proteins as part of an alternative DNA excision repair pathway

Jung Hoon Yoon, Piotr M. Swiderski, Bruce E. Kaplan, Masashi Takao, Akira Yasui, Binghui Shen, Gerd P. Pfeifer

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

Ultraviolet (UV) irradiation induces predominantly cyclobutane and (6- 4) pyrimidine dimer photoproducts in DNA. Several mechanisms for repairing these mutagenic UV-induced DNA lesions have been identified. Nucleotide excision repair is a major pathway, but mechanisms involving photolyases and DNA glycosylases have also been characterized. Recently, a novel UV damage endonuclease (UVDE) was identified that initiates an excision repair pathway different from previously established repair mechanisms. Homologues of UVDE have been found in eukaryotes as well as in bacteria. In this report, we have used oligonucleotide substrates containing site-specific cyclobutane pyrimidine dimers and (6-4) photoproducts for the characterization of this UV damage repair pathway. After introduction of single-strand breaks at the 5' sides of the photolesions by UVDE, these intermediates became substrates for cleavage by flap endonucleases (FEN-1 proteins). FEN-1 homologues from humans, Saccharomyces cerevisiae, and Schizosaccharomyces pombe all cleaved the UVDE-nicked substrates at similar positions 3' to the photolesions. T4 endonuclease V-incised DNA was processed in the same way. Both nicked and flapped DNA substrates with photolesions (the latter may be intermediates in DNA polymerase-catalyzed strand displacement synthesis) were cleaved by FEN- 1. The data suggest that the two enzymatic activities, UVDE and FEN-1, are part of an alternative excision repair pathway for repair of UV photoproducts.

Original languageEnglish
Pages (from-to)4809-4817
Number of pages9
JournalBiochemistry
Volume38
Issue number15
DOIs
Publication statusPublished - 1999 Apr 13

ASJC Scopus subject areas

  • Biochemistry

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