Requirement of yeast RAD2, a homolog of human XPG gene, for efficient cell cycle regulation in the presence of UV damage

초록

Mutations in the human XPG gene cause Cockayne syndrome (CS). In addition to increased photosensitivity, CS patients suffer from severe developmental abnormalities, including growth retardation, mental retardation, and premature aging. Wheras a deficiency in the preferential repair of UV lesions from the transcribed strand accounts for the increased photosensitivity of CS patients, the reason for developmental defects in these individuals has remained unclear. RAD2, the S. cerevisiae counterpart of XPG, was shown to be involved in promoting efficient RNA polymerase II transcription in the absence of DNA damage. However, its function in developmental abnormalities in the presence of DNA damage has not been tested. Recemtly, we showed that overexpression of Rad2p causes mitotic catastrophe in RAD9-dependent manner. The result implies that RAD2 functions in cell cycle regulation. Here, we examined the effects of various RAD2 mutations on cell cycle progression and morphological changes in the presence and absence of DNA damage. The RAD2 C-terminal mutations cause abettant cell cycle arrest and morphological changes after UV irradiation. These results provide evidence for the involvement of RAD2 in efficient cell cycle regulation in the presence of DNA damage. From these and other observations presented here, we suggest that cell cycle defects triggered by UV damage are the underlying cause of CS.