Around and beyond 53BP1 Nuclear Bodies

Int J Mol Sci. 2017 Dec 5;18(12):2611. doi: 10.3390/ijms18122611.

Abstract

Within the nucleus, sub-nuclear domains define territories where specific functions occur. Nuclear bodies (NBs) are dynamic structures that concentrate nuclear factors and that can be observed microscopically. Recently, NBs containing the p53 binding protein 1 (53BP1), a key component of the DNA damage response, were defined. Interestingly, 53BP1 NBs are visualized during G1 phase, in daughter cells, while DNA damage was generated in mother cells and not properly processed. Unlike most NBs involved in transcriptional processes, replication has proven to be key for 53BP1 NBs, with replication stress leading to the formation of these large chromatin domains in daughter cells. In this review, we expose the composition and organization of 53BP1 NBs and focus on recent findings regarding their regulation and dynamics. We then concentrate on the importance of the replication stress, examine the relation of 53BP1 NBs with DNA damage and discuss their dysfunction.

Keywords: 53BP1; DNA damage; cancer; common fragile sites; genetic instability; nuclear bodies; replication stress.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Nucleus / metabolism
  • Chromatin / metabolism
  • DNA Damage / genetics
  • DNA Damage / physiology*
  • DNA Replication / genetics
  • DNA Replication / physiology
  • Humans
  • Tumor Suppressor p53-Binding Protein 1 / genetics
  • Tumor Suppressor p53-Binding Protein 1 / metabolism*

Substances

  • Chromatin
  • TP53BP1 protein, human
  • Tumor Suppressor p53-Binding Protein 1