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Nat Commun. 2017 Oct 17;8(1):985. doi: 10.1038/s41467-017-01151-w.

AUNIP/C1orf135 directs DNA double-strand breaks towards the homologous recombination repair pathway.

Author information

1
Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
2
Huadong Research Institute for Medicine and Biotechniques, Nanjing, Jiangsu, 210002, China.
3
School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Pok Fu Lam, Hong Kong, China.
4
Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.
5
Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, 310058, China. jhuang@zju.edu.cn.

Abstract

DNA double-strand breaks (DSBs) are mainly repaired by either homologous recombination (HR) or non-homologous end-joining (NHEJ). Here, we identify AUNIP/C1orf135, a largely uncharacterized protein, as a key determinant of DSB repair pathway choice. AUNIP physically interacts with CtIP and is required for efficient CtIP accumulation at DSBs. AUNIP possesses intrinsic DNA-binding ability with a strong preference for DNA substrates that mimic structures generated at stalled replication forks. This ability to bind DNA is necessary for the recruitment of AUNIP and its binding partner CtIP to DSBs, which in turn drives CtIP-dependent DNA-end resection and HR repair. Accordingly, loss of AUNIP or ablation of its ability to bind to DNA results in cell hypersensitivity toward a variety of DSB-inducing agents, particularly those that induce replication-associated DSBs. Our findings provide new insights into the molecular mechanism by which DSBs are recognized and channeled to the HR repair pathway.DNA double strand breaks can be repaired by homology-independent or homology-directed mechanisms. The choice between these pathways is a key event for genomic stability maintenance. Here the authors identify and characterize AUNIP, as a factor involved in tilting the balance towards homology repair.

PMID:
29042561
PMCID:
PMC5645412
DOI:
10.1038/s41467-017-01151-w
[Indexed for MEDLINE]
Free PMC Article

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