A role of yeast Rad2p in lifespan and mutagenesis regulation by cell cycle and actin dynamics regulation

초록

The xeroderma pigmentosum group G (XPG) gene, encoding an essential element in nucleotide excision repair (NER), has a proliferating cell nuclear antigen-binding domain (PCNA-BD) at its C-terminal region. Mutations in the human XPG gene cause Cockayne syndrome (CS) and xeroderma pigmentosum (XP). By applying genetic and biochemical approaches, we have analyzed the role of RAD2, the Saccharomyces cerevisiae counterpart of XPG, in the unknown cellular functions. Rad2p interacts with PCNA through its PCNA-BD and the PCNA-BD of Rad2p plays a role in UV-induced mutagenesis. Our results provide evidences indicating that the Rad2p-PCNA interaction might be responsible for mutagenesis control in the general NER pathway. In addition we characterized the mutational phenotypes of RAD2 C-terminal deletion, which resembles the XPG mutation found in XPG/CS cells. RAD2 C-terminal deletion caused cell growth arrest, the cell cycle stalling, a defective a-factor response, shortened lifespan, cell polarity defect, and misregulated actin-dynamics after DNA damage. These results provide insights into the role of RAD2 in post-UV irradiation cell cycle regulation and actin assembly, which may be an underlying cause of XPG/CS.