Novel function of yeast RAD2 in cell cycle and cell polarity that affects yeast lifespan

초록

Cockayne syndrome (CS) is a human hereditary disorder characterized by retarded growth, impaired neurological development, mental retardation and premature aging without cancer predisposition. Mutations in the CSA, CSB, XPB, XPD and XPG genes cause CS. These genes are involved in transcription and transcription-coupled nucleotide excision repair (TC-NER) that removes DNA lesions on the actively transcribed DNA strand. Failure of the TC-NER causes not only accumulation of unrepaired DNA but also block transcription.Therefore, CS has been considered as a transcription syndrome. Nevertheless, it is still elusive to define the cause of CS because transcription defect alone can not explain many of the clinical features of CS. Yeast RAD2, a counterpart of human XPG, is an essential gene for nucleotide excision repair and TC-NER. Using the rad2 C-terminal deletion mutants which mimick XPG mutations in XPG/CS patients, we found that the rad2 C-terminal deletion mutation causes cell growth retardation, sterility and shortened lifespan after UV irradiation. In addition, the rad2 C-terminal deletion mutant produces cells with enlarged morphology and disorganized actin patches after UV irradiation. On the other hand, Rad2p over-expression caused hyper-polarization. These results demonstrate that the Rad2p C-terminal region has a role in cell cycle and cell polarity regulation.