Global Genome Nucleotide Excision Repair Proteins Rhp7p and Rhp41p Are Involved in Abasic Site Repair of <i>Schizosaccharomyces pombe</i>

Abstract

The roles of nucleotide excision repair (NER) proteins in removing UV-induced lesions are well defined. There are two distinct NER pathways: global genome NER (GG-NER) and transcription-coupled NER. In human GG-NER, two heteromeric protein complexes, DDB1-DDB2 and XPC-RAD23, are responsible for initial lesion recognition. Here, we examined the genetic interactions between GG-NER and base excision repair (BER) genes during abasic (AP) site repair of Schizosaccharomyces pombe . Mutants of rhp7 ( rhp7-rhp16 are functional homologs of DDB1-DDB2 ) and rhp 41 (XPC homolog) were moderately sensitive to methyl methanesulfonate and slightly to sodium bisulfite. Nth1p most actively cleaves the AP site in S. pombe . Deletion of rhp7 or rhp 41 from nth1 &#916 cells greatly increased their sensitivity to alkylation and deamination, indicating that Rhp7p and Rhp41p are involved in repair of the AP sites generated by the action of DNA glycosylase. Induction of rhp 7 and rhp 16 genes by different types of DNA damage supports the ability of GG-NER to remove non-bulky lesions. Therefore, GG-NER activity not only targets bulky DNA helix-distorting lesions, but can also efficiently remove AP sites synergistically with BER.