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Haibo Wang, Ailian Zhao, Lin Chen, Xueyan Zhong, Ji Liao, Min Gao, Minghua Cai, Dong-Hyun Lee, Jing Li, Dipanjan Chowdhury, Yun-gui Yang, Gerd P. Pfeifer, Yun Yen, Xingzhi Xu, Human RIF1 encodes an anti-apoptotic factor required for DNA repair , Carcinogenesis, Volume 30, Issue 8, August 2009, Pages 1314–1319, https://doi.org/10.1093/carcin/bgp136
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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.
- apoptosis
- mutation
- ataxia-telangiectasia
- breast neoplasms
- camptothecin
- infiltrating duct carcinoma
- caspases
- dna
- dna damage
- dna repair
- recombination, genetic
- s phase
- staurosporine
- antibodies
- breast
- cancer therapy
- cytokinesis
- rna, small interfering
- double strand break repair
- cell cycle checkpoint
- double-stranded dna breaks
- tumor cells, malignant