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Carcinogenesis Advance Access published online on May 29, 2009
Carcinogenesis, doi:10.1093/carcin/bgp136
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Haibo Wang1,#, Ailian Zhao2,#, Lin Chen1,#, Xueyan Zhong3, Ji Liao1, Min Gao4, Minghua Cai1, Dong-Hyun Lee5, Jing Li1, Dipanjan Chowdhury5, Yun-gui Yang4, Gerd P. Pfeifer3, Yun Yen6 and Xingzhi Xu1,*

1 Laboratory of Cancer Biology, College of Life Sciences, Capital Normal University, Beijing 100048, China
2 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing 100142, China
3 Division of Biology, City of Hope National Medical Center, Duarte, CA 91010, USA
4 Genome Stability Group, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China
5 Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
6 Division of Molecular and Clinical Pharmacology, City of Hope National Medical Center, Duarte, CA 91010, USA

* Corresponding author: Xingzhi (Xavier) Xu, PhD, Laboratory of Cancer Biology, College of Life Sciences, Capital Normal University, 105 Xi San Huan Road (N), Beijing 100048, China. Tel: 86-10-68902440; Fax: 86-10-68906307; Email: Xingzhi_Xu{at}mail.cnu.edu.cn

Human RIF1 (Rap1 interacting protein 1) contributes to the ATM-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 siRNA 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.

Key Words: human RIF1 • DNA double-strand break • homologous recombination • apoptosis • breast cancer

# these authors contributed equally to this work.

Received April 16, 2009; revised May 12, 2009; accepted May 20, 2009.


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