RIF1 and PAX1IP bind TP53BP1 at DNA DSBs

Stable Identifier
Reaction [dissociation]
Homo sapiens
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RIF1 binds TP53BP1 phosphorylated by ATM at DNA double strand breaks (DSBs). RIF1 binding interferes with the accumulation of BRCA1:BARD1 heterodimers and associated proteins at DNA DSBs. Therefore, TP53BP1-mediated recruitment of RIF1 prevents RBBP8 (CtIP) binding to BRCA1:BARD1 and the subsequent resection of DNA DSBs. The action of RIF1 and TP53BP1 promotes non-homologous end joining (NHEJ) of DNA DSBs during G1 phase of the cell cycle, when sister chromatids are not available for homologous recombination-mediated repair (Zimmermann et al. 2013, Escribano-Diaz et al. 2013).

Similar to RIF1, PAX1IP (PTIP) is also recruited to DNA DSBs through interaction with ATM-phosphorylated TP53BP1. Since RIF1 and PAX1IP interact with different phosphorylated sites on TP53BP1, they can simultaneously bind TP53BP1 and colocalize in the majority of TP53BP1 foci. PAX1IP contributes to inhibition of DNA DSB resection mediated by BRCA1-recruited RBBP8 (CtIP) (Callen et al. 2013).

Literature References
PubMed ID Title Journal Year
23727112 53BP1 mediates productive and mutagenic DNA repair through distinct phosphoprotein interactions

Ge, K, Callen, E, Daniel, JA, Polato, F, Alt, FW, Wesemann, DR, Wong, N, Fernandez-Capetillo, O, Chen, HT, Kruhlak, MJ, Sleckman, BP, Nussenzweig, MC, Starnes, LM, Di Virgilio, M, Lee, JE, Nieto-Soler, M, Santos, M, Faryabi, RB, Tubbs, A, Nussenzweig, A

Cell 2013
23333306 A cell cycle-dependent regulatory circuit composed of 53BP1-RIF1 and BRCA1-CtIP controls DNA repair pathway choice

Durocher, D, Canny, MD, Fradet-Turcotte, A, Tká?, J, Xing, M, Rosebrock, AP, Cook, MA, Orthwein, A, Munro, M, Young, JT, Escribano-Díaz, C, Xu, D

Mol. Cell 2013
23306437 53BP1 regulates DSB repair using Rif1 to control 5' end resection

Zimmermann, M, Buonomo, SB, de Lange, T, Lottersberger, F, Sfeir, A

Science 2013
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