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PMID: 19483192 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Human RIF1 encodes an anti-apoptotic factor required for DNA repair.

Carcinogenesis ·Vol. 30 ·No. 8 ·2009-08-00 ·Pages 1314-9

Wang H, Zhao A, Chen L, Zhong X, Liao J, Gao M, Cai M, Lee DH, Li J, Chowdhury D, Yang YG, Pfeifer GP, Yen Y, Xu X

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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18 references, click to expand
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Article Info
Journal
Carcinogenesis
Abbr.
Carcinogenesis
ISSN
1460-2180
Published
2009-08-00
Epub
2009-00-29
Pages
1314-9
Language
English
Region
England
NLM ID
8008055
PMCID
PMC2718077
Subset
IM
Grants
NCI NIH HHS · R01CA084469 · United States
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