Rad2p modulates mutagenesis after UV exposure via interaction with PCNA

초록

Yeast RAD2, a homolog of the human xeroderma pigmentosum group G gene (XPG), has a Proliferating Cell Nuclear Antigen (PCNA)-binding motif at the C-terminal region. However, the role of this motif is controversial because its presence does not affect nucleotide excision repair. In this study, we show that Rad2p PCNA-binding motif is important for its interaction with PCNA, and the mutation of the PCNA-binding motif in Rad2p causes UV-induced mutagenesis increase. On the other hand, impairment of the motif decreased mutation rates after UV irradiation in the presence of other NER-related gene defects. Also, Rad2p-PCNA interaction induced cell cycle arrest resulting in cell growth retardation after UV irradiation. These observations suggest that the drastically increased skin cancer incidence in xeroderma pigmentosum could arise from the synergistic effects between cell cycle arrest by XPG–PCNA interaction and the accumulation of damaged DNA via defects in DNA damage repair.