Abstract
Human Rap1-interacting protein 1 (RIF1) contributes to the ataxia telangiectasia, mutated-mediated DNA damage response against the dexterous effect of DNA lesions and plays a critical role in the S-phase checkpoint. However, the molecular mechanisms by which human RIF1 conquers DNA aberrations remain largely unknown. We here showed that inhibition of RIF1 expression by small interfering RNA led to defective homologous recombination-mediated DNA double-strand break repair and sensitized cancer cells to camptothecin or staurosporine treatment. RIF1 underwent caspase-dependent cleavage upon apoptosis. We further found that RIF1 was highly expressed in human breast tumors, and its expression status was positively correlated with differentiation degrees of invasive ductal carcinoma of the breast. Our results suggest that RIF1 encodes an anti-apoptotic factor required for DNA repair and is a potential target for cancer treatment.
MeSH Terms
Apoptosis/drug effects
Blotting, Western
Breast Neoplasms/drug therapy,metabolism,pathology
Camptothecin/therapeutic use
Carcinoma, Ductal, Breast/drug therapy,metabolism,pathology
Cell Differentiation
Cell Proliferation
DNA Breaks, Double-Stranded
DNA Repair
Enzyme Inhibitors/pharmacology
Female
Humans
Immunoenzyme Techniques
Immunoprecipitation
Nuclear Proteins/physiology
Nuclear Receptor Co-Repressor 1
RNA, Small Interfering/pharmacology
Repressor Proteins/physiology
Signal Transduction/drug effects
Staurosporine/therapeutic use
Tumor Cells, Cultured
Chemicals
Enzyme Inhibitors
NCOR1 protein, human
Nuclear Proteins
Nuclear Receptor Co-Repressor 1
RNA, Small Interfering
Repressor Proteins
Staurosporine
Camptothecin
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Wang Haibo
Laboratory of Cancer Biology, College of Life Sciences, Capital Normal University, Beijing 100048, China.
Zhao Ailian
Chen Lin
Zhong Xueyan
Liao Ji
Gao Min
Cai Minghua
Lee Dong-Hyun
Li Jing
Chowdhury Dipanjan
Yang Yun-gui
Pfeifer Gerd P
Yen Yun
Xu Xingzhi
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