title: Checkpoint protein Rad9 plays an important role in nucleotide excision repair.
abstract: Rad9, an evolutionarily conserved checkpoint gene with multiple functions for preserving genomic integrity, has been shown to play important roles in homologous recombination repair, base excision repair and mismatch repair. However, whether Rad9 has an impact on nucleotide excision repair remains unknown. Here we demonstrated that Rad9 was involved in nucleotide excision repair and loss of Rad9 led to defective removal of the UV-derived photoproduct 6-4PP (6,4 pyrimidine-pyrimidone) and the BPDE (anti-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide)-DNA adducts in mammalian cells. We also demonstrated that Rad9 could co-localize with XPC in response to local UV irradiation. However, our data showed that Rad9 was not required for the photoproducts recognition step of nucleotide excision repair. Further investigation revealed that reduction of Rad9 reduced the UV-induced transcription of the genes of the nucleotide excision repair factors DDB2, XPC, DDB1 and XPB and DDB2 protein levels in human cells. Interestingly, knockdown of one subunit of DNA damage recognition complex, hHR23B impaired Rad9-loading onto UV-damaged chromatin. Based on these results, we suggest that Rad9 plays an important role in nucleotide excision repair through mechanisms including maintaining DDB2 protein level in human cells.
authors: Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Tiepeng
authors: T
authors: Li
authors: Zhixin
authors: Z
authors: Wang
authors: Yun
authors: Y
authors: Zhao
authors: Wei
authors: W
authors: He
authors: Lili
authors: L
authors: An
authors: Shengquan
authors: S
authors: Liu
authors: Yuheng
authors: Y
authors: Liu
authors: Hailin
authors: H
authors: Wang
authors: Haiying
authors: H
authors: Hang
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D053595:Embryonic Stem Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D021381:Protein Transport; D011740:Pyrimidine Dimers / Q000378:metabolism; D034741:RNA, Small Interfering; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; C117669:DDB2 protein, human; D018736:DNA Adducts; D004268:DNA-Binding Proteins; D011740:Pyrimidine Dimers; D034741:RNA, Small Interfering; C058406:pyrimidine-pyrimidone dimer; C069930:rad9 protein; C086984:XPC protein, human; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide