Review Volume 11, Issue 8 pp 2488—2511

A role of the 53BP1 protein in genome protection: structural and functional characteristics of 53BP1-dependent DNA repair

Eva Bártová 1, , Soňa Legartová 1, , Miroslav Dundr 2, , Jana Suchánková 1, ,

  • 1 Institute of Biophysics of the Czech Academy of Sciences, 612 65 Brno, Czech Republic
  • 2 Rosalind Franklin University of Medicine and Science, Chicago Medical School, Department of Cell Biology, North Chicago, IL 60064, USA

received: January 6, 2019 ; accepted: April 10, 2019 ; published: April 17, 2019 ;
How to Cite

Copyright: Bártová et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Nuclear architecture plays a significant role in DNA repair mechanisms. It is evident that proteins involved in DNA repair are compartmentalized in not only spontaneously occurring DNA lesions or ionizing radiation-induced foci (IRIF), but a specific clustering of these proteins can also be observed within the whole cell nucleus. For example, 53BP1-positive and BRCA1-positive DNA repair foci decorate chromocenters and can appear close to nuclear speckles. Both 53BP1 and BRCA1 are well-described factors that play an essential role in double-strand break (DSB) repair. These proteins are members of two protein complexes: 53BP1-RIF1-PTIP and BRCA1-CtIP, which make a “decision” determining whether canonical nonhomologous end joining (NHEJ) or homology-directed repair (HDR) is activated. It is generally accepted that 53BP1 mediates the NHEJ mechanism, while HDR is activated via a BRCA1-dependent signaling pathway. Interestingly, the 53BP1 protein appears relatively quickly at DSB sites, while BRCA1 is functional at later stages of DNA repair, as soon as the Mre11-Rad50-Nbs1 complex is recruited to the DNA lesions. A function of the 53BP1 protein is also linked to a specific histone signature, including phosphorylation of histone H2AX (γH2AX) or methylation of histone H4 at the lysine 20 position (H4K20me); therefore, we also discuss an epigenetic landscape of 53BP1-positive DNA lesions.


Act-D: actinomycin D; ATM: Ataxia telangiectasia-mutated kinase; BER: base excision repair; BRCT: BRCA1 C terminus; CBs: Cajal bodies; CPDs: cyclobutane pyrimidine dimers; CPT: camptothecin; CDK 1: cyclin-dependent kinase 1; DDR: DNA damage response; DNA-PKcs: DNA-dependent protein kinases; ESC: embryonic stem cells; FRAP: fluorescence recovery after photobleaching; HAT: histone acetyltransferases; HDAC: histone deacetylase; HDACi: inhibitor of histone deacetylase; HP1: heterochromatin protein 1; HDR: homology-directed repair; IGAZ: interchromatin granule-associated zones; IRIF: ionizing radiation induced foci; MDC1: mediator of DNA damage checkpoint 1; MRN: Mre11-Rad50-Nbs1 protein complex; NBs: nuclear bodies; NER: nucleotide excision repair; NHEJ: non-homologous end joining; NBS: Nibrin; PARP: poly(ADP-ribose) polymerase; PcG: polycomb group proteins; PML: promyelocytic leukemia bodies; PRC2: polycomb repressive complex 2; PTIP: Pax transactivation domain-interacting protein; RAP1: interacting factor 1 (RIF1); RNA Pol I: RNA Polymerase I; SIM: structured illumination microscopy; STED: stimulated emission depletion; TCOF-1: Treacle protein 1; TCR: transcription coupled-DSB repair; TTD: tandem Tudor domain; UBF: upstream binding factor; UV light: ultraviolet light; γH2AX: histone H2AX, serine 139 phosphorylation.