Telomere-associated protein RIF1

Definition:

Key regulator of TP53BP1 that plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage: acts by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs. In response to DNA damage, interacts with ATM-phosphorylated TP53BP1. Interaction with TP53BP1 leads to dissociate the interaction between NUDT16L1/TIRR and TP53BP1, thereby unmasking the tandem Tudor-like domain of TP53BP1 and allowing recruitment to DNA DSBs. Once recruited to DSBs, RIF1 and TP53BP1 act by promoting NHEJ-mediated repair of DSBs. In the same time, RIF1 and TP53BP1 specifically counteract the function of BRCA1 by blocking DSBs resection via homologous recombination (HR) during G1 phase. Also required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (By similarity). Promotes NHEJ of dysfunctional telomeres (By similarity).

References:

[1]. Pascal Drané, et al. TIRR regulates 53BP1 by masking its histone methyl-lysine binding function. Nature. 2017 Mar 9;543(7644):211-216. [Content Brief]

[2]. Cristina Escribano-Díaz, et al. A cell cycle-dependent regulatory circuit composed of 53BP1-RIF1 and BRCA1-CtIP controls DNA repair pathway choice. Mol Cell. 2013 Mar 7;49(5):872-83. [Content Brief]

[3]. Joshua Silverman, et al. Human Rif1, ortholog of a yeast telomeric protein, is regulated by ATM and 53BP1 and functions in the S-phase checkpoint. Genes Dev. 2004 Sep 1;18(17):2108-19. [Content Brief]

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