Evidence for the involvement of nucleotide excision repair in the removal of abasic sites in yeast

Carlos A. Torres-Ramos, Robert E. Johnson, Louise Prakash, Satya Prakash

Research output: Contribution to journalArticle

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Abstract

In eukaryotes, DNA damage induced by ultraviolet light and other agents which distort the helix is removed by nucleotide excision repair (NER) in a fragment ~25 to 30 nucleotides long. In humans, a deficiency in NER causes xeroderma pigmentosum (XP), characterized by extreme sensitivity to sunlight and a high incidence of skin cancers. Abasic (AP) sites are formed in DNA as a result of spontaneous base loss and from the action of DNA glycosylases involved in base excision repair. In Saccharomyces cerevisiae, AP sites are removed via the action of two class II AP endonucleases, Apn1 and Apn2. Here, we provide evidence for the involvement of NER in the removal of AP sites and show that NER competes with Apn1 and Apn2 in this repair process. Inactivation of NER in the apn1Δ or apn1Δ apn2Δ strain enhances sensitivity to the monofunctional alkylating agent methyl methanesulfonate and leads to further impairment in the cellular ability to remove AP sites. A deficiency in the repair of AP sites may contribute to the internal cancers and progressive neurodegeneration that occur in XP patients.

Original languageEnglish (US)
Pages (from-to)3522-3528
Number of pages7
JournalMolecular and Cellular Biology
Volume20
Issue number10
DOIs
StatePublished - May 1 2000

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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