NDR1 modulates the UV-induced DNA-damage checkpoint and nucleotide excision repair.
Nucleotide excision repair (NER) is the sole mechanism of UV-induced DNA lesion repair in mammals. A single round of NER requires multiple components including seven core NER factors, xeroderma pigmentosum A-G (XPA-XPG), and many auxiliary effector proteins including ATR serine/threonine kinase. The XPA protein helps to verify DNA damage and thus plays a rate-limiting role in NER. Hence, the regulation of XPA is important for the entire NER kinetic. We found that NDR1, a novel XPA-interacting protein, modulates NER by modulating the UV-induced DNA-damage checkpoint. In quiescent cells, NDR1 localized mainly in the cytoplasm. After UV irradiation, NDR1 accumulated in the nucleus. The siRNA knockdown of NDR1 delayed the repair of UV-induced cyclobutane pyrimidine dimers in both normal cells and cancer cells. It did not, however, alter the expression levels or the chromatin association levels of the core NER factors following UV irradiation. Instead, the NDR1-depleted cells displayed reduced activity of ATR for some set of its substrates including CHK1 and p53, suggesting that NDR1 modulates NER indirectly via the ATR pathway.
Department of Biological Science, Dong-A University, Busan, South Korea.
Jeong-Min
JM
Park
Department of Biological Science, Dong-A University, Busan, South Korea.
Ji Ye
JY
Choi
Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, South Korea.
Joo Mi
JM
Yi
Department of Biological Science, Dong-A University, Busan, South Korea.
Jin Woong
JW
Chung
Department of Biological Science, Dong-A University, Busan, South Korea.
Sun-Hee
SH
Leem
Department of Biological Science, Dong-A University, Busan, South Korea.
Sang Seok
SS
Koh
Department of Biological Science, Dong-A University, Busan, South Korea. Electronic address: thkang@dau.ac.kr.
Tae-Hong
TH
Kang
D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering; D014466:Ultraviolet Rays
D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D017346:Protein Serine-Threonine Kinases; C491614:STK38 protein, human
ATR; NDR1; Nucleotide excision repair; UV; XPA