Molecular Mechanisms of DNA Damage Recoguition and Repair

点击翻译按钮获取中文摘要

We previously isolated a protein complex which biochemically corrects the defect of XP-C cell extracts in nucleotide excision repair (NER) in vitro. In the present study, we have analyzed the functions of the protein complex, XPC/HHR23B, in NER in mammalian cells and obtained the following results.1) In mouse cells, there are homologues of human XPC/HHR23B and another RAD23 homologue, HHR23A.They have quite high homologies with each other.2) We found most of XPC, HHR23B and HHR23A in nucleus. They do not make a tight complex with other NER proteins.3) HHR23B stimulates the NER activity of XPC protein in vitro.4) HHR23A protein makes a complex with HIV-1 Vpr protein and affects the cell cycle progression.5) A very limited region of HHR23B is necessary and sufficient for XPC binding as well as the stimulation of NER activity of XPC.6) HHR23A could reconstitute a physical complex with XPC and stimulate the in vitro repair activity in place of HHR23B.7) XPC/HHR23B complex works as the earliest damage detector to initiate global genome repair subpathway of NER.8) We found that a component of 26S proteasome, S5a, associates with HHR23B in yeast two-hybrid system as well as in crude cell extracts.