Human RIF1 encodes an anti-apoptotic factor required for DNA repair.
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.
Wang
Haibo
H
Laboratory of Cancer Biology, College of Life Sciences, Capital Normal University, Beijing 100048, China.
Zhao
Ailian
A
Chen
Lin
L
Zhong
Xueyan
X
Liao
Ji
J
Gao
Min
M
Cai
Minghua
M
Lee
Dong-Hyun
DH
Li
Jing
J
Chowdhury
Dipanjan
D
Yang
Yun-gui
YG
Pfeifer
Gerd P
GP
Yen
Yun
Y
Xu
Xingzhi
X
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002166:Camptothecin / Q000627:therapeutic use; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D009687:Nuclear Proteins / Q000502:physiology*; D056971:Nuclear Receptor Co-Repressor 1; D034741:RNA, Small Interfering / Q000494:pharmacology; D012097:Repressor Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; C539127:NCOR1 protein, human; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D019311:Staurosporine; D002166:Camptothecin