NDR1 modulates the UV-induced DNA-damage checkpoint and nucleotide excision repair

Journal Article · Fri Jun 05 04:00:00 EDT 2015 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2015.04.071· OSTI ID:22462073

Park, Jeong-Min; Choi, Ji Ye ^[1]; Yi, Joo Mi ^[2]; Chung, Jin Woong; Leem, Sun-Hee; Koh, Sang Seok ^[1]; Kang, Tae-Hong ^[1]

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1. Department of Biological Science, Dong-A University, Busan (Korea, Republic of)
2. Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan (Korea, Republic of)

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. - Highlights: • NDR1 is a novel XPA-interacting protein. • NDR1 accumulates in the nucleus in response to UV irradiation. • NDR1 modulates NER (nucleotide excision repair) by modulating the UV-induced DNA-damage checkpoint response.

• OSTI ID: 22462073
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 461; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CHROMATIN
CONGENITAL DISEASES
CYTOPLASM
DNA
DNA DAMAGES
EXCISION REPAIR
HEREDITARY DISEASES
IRRADIATION
MAMMALS
NEOPLASMS
NUCLEOTIDES
PROTEINS
PYRIMIDINE DIMERS
SERINE
SKIN DISEASES
THREONINE