Lombaerts M, Goeloe J I, den Dulk H, Brandsma J A, Brouwer J
Medical Genetics Centre South-West Netherlands, Leiden University, Leiden, 2300 RA, The Netherlands.
Biochem Biophys Res Commun. 2000 Feb 5;268(1):210-5. doi: 10.1006/bbrc.2000.2100.
We have identified rhp23(+), the ortholog of the Saccharomyces cerevisiae RAD23 and human HHR23A and HHR23B genes, in Schizosaccharomyces pombe and examined its role in cell survival and DNA repair. In S. pombe two repair mechanisms are operative on UV-induced photoproducts, i.e., UV damage repair (UVDR) and nucleotide excision repair (NER). Here we show that Rhp23 is solely involved in NER and study its role in DNA repair in the absence of the UVDR pathway. S. pombe rhp23-deficient cells are sensitive toward UV irradiation, although not as sensitive as complete NER-deficient cells. Furthermore we demonstrate that the residual survival observed in rhp23-deficient cells is NER dependent. Despite this NER-dependent survival, uvde rhp23 double mutants are unable to repair cyclobutane pyrimidine dimers. The inability to remove these photolesions from both DNA strands clearly demonstrates that rhp23(+) is involved in transcription coupled repair as well as global genome repair.
我们在粟酒裂殖酵母中鉴定出了rhp23(+),它是酿酒酵母RAD23以及人类HHR23A和HHR23B基因的直系同源基因,并研究了其在细胞存活和DNA修复中的作用。在粟酒裂殖酵母中,有两种修复机制作用于紫外线诱导的光产物,即紫外线损伤修复(UVDR)和核苷酸切除修复(NER)。在此我们表明,Rhp23仅参与NER,并研究了其在缺乏UVDR途径时在DNA修复中的作用。粟酒裂殖酵母中缺乏rhp23的细胞对紫外线照射敏感,尽管不如完全缺乏NER的细胞敏感。此外,我们证明在缺乏rhp23的细胞中观察到的残余存活是依赖NER的。尽管有这种依赖NER的存活情况,但uvde rhp23双突变体无法修复环丁烷嘧啶二聚体。无法从两条DNA链上去除这些光损伤清楚地表明,rhp23(+)参与了转录偶联修复以及全基因组修复。