TP53-binding protein 1

Definition:

Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis. Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1. In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites. Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites. Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs. Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1.

References:

[1]. Bin Wang, et al. 53BP1, a mediator of the DNA damage checkpoint. Science. 2002 Nov 15;298(5597):1435-8. [Content Brief]

[2]. 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]

[3]. Amélie Fradet-Turcotte, et al. 53BP1 is a reader of the DNA-damage-induced H2A Lys 15 ubiquitin mark. Nature. 2013 Jul 4;499(7456):50-4. [Content Brief]

[4]. Yoonsung Kang, et al. Protein phosphatase 5 is necessary for ATR-mediated DNA repair. Biochem Biophys Res Commun. 2011 Jan 7;404(1):476-81. [Content Brief]

[5]. Elsa Callen, et al. 53BP1 mediates productive and mutagenic DNA repair through distinct phosphoprotein interactions. Cell. 2013 Jun 6;153(6):1266-80. [Content Brief]

[6]. Francisca Lottersberger, et al. Role of 53BP1 oligomerization in regulating double-strand break repair. Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2146-51. [Content Brief]

[7]. J Ross Chapman, et al. BRCA1-associated exclusion of 53BP1 from DNA damage sites underlies temporal control of DNA repair. J Cell Sci. 2012 Aug 1;125(Pt 15):3529-34. [Content Brief]

[8]. Maria Victoria Botuyan, et al. Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. Cell. 2006 Dec 29;127(7):1361-73. [Content Brief]

[9]. Karine Jacquet, et al. The TIP60 Complex Regulates Bivalent Chromatin Recognition by 53BP1 through Direct H4K20me Binding and H2AK15 Acetylation. Mol Cell. 2016 May 5;62(3):409-421. [Content Brief]

[10]. 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]

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