DNA endonuclease RBBP8

Definition:

Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in DNA-end resection, the first step of double-strand break (DSB) repair through the homologous recombination (HR) pathway. HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse. Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ). Functions downstream of the MRN complex and ATM, promotes ATR activation and its recruitment to DSBs in the S/G2 phase facilitating the generation of ssDNA. Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage. During immunoglobulin heavy chain class-switch recombination, promotes microhomology-mediated alternative end joining (A-NHEJ) and plays an essential role in chromosomal translocations (By similarity).

References:

[1]. Alessandro A Sartori, et al. Human CtIP promotes DNA end resection. Nature. 2007 Nov 22;450(7169):509-14. [Content Brief]

[2]. Zhongsheng You, et al. CtIP links DNA double-strand break sensing to resection. Mol Cell. 2009 Dec 25;36(6):954-69. [Content Brief]

[3]. Xiaochun Yu, et al. BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP. Genes Dev. 2006 Jul 1;20(13):1721-6. [Content Brief]

[4]. Feng Liu, et al. CtIP activates its own and cyclin D1 promoters via the E2F/RB pathway during G1/S progression. Mol Cell Biol. 2006 Apr;26(8):3124-34. [Content Brief]

[5]. Pablo Huertas, et al. Human CtIP mediates cell cycle control of DNA end resection and double strand break repair. J Biol Chem. 2009 Apr 3;284(14):9558-65. [Content Brief]

[6]. Jingsong Yuan, et al. N terminus of CtIP is critical for homologous recombination-mediated double-strand break repair. J Biol Chem. 2009 Nov 13;284(46):31746-52. [Content Brief]

[7]. Annika Baude, et al. Hepatoma-derived growth factor-related protein 2 promotes DNA repair by homologous recombination. Nucleic Acids Res. 2016 Mar 18;44(5):2214-26. [Content Brief]

[8]. Xiaochun Yu, et al. DNA damage-induced cell cycle checkpoint control requires CtIP, a phosphorylation-dependent binding partner of BRCA1 C-terminal domains. Mol Cell Biol. 2004 Nov;24(21):9478-86. [Content Brief]

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