Spatiotemporal regulation of posttranslational modifications in the DNA damage response

EMBO J. 2016 Jan 4;35(1):6-23. doi: 10.15252/embj.201592595. Epub 2015 Dec 1.

Abstract

A timely and accurate cellular response to DNA damage requires tight regulation of the action of DNA damage response (DDR) proteins at lesions. A multitude of posttranslational modifications (PTMs) of chromatin and chromatin-associated proteins coordinates the recruitment of critical proteins that dictate the appropriate DNA repair pathway and enable the actual repair of lesions. Phosphorylation, ubiquitylation, SUMOylation, neddylation, poly(ADP-ribosyl)ation, acetylation, and methylation are among the DNA damage-induced PTMs that have taken center stage as important DDR regulators. Redundant and multivalent interactions of DDR proteins with PTMs may not only be a means to facilitate efficient relocalization, but also a feature that allows high temporal and spatial resolution of protein recruitment to, and extraction from, DNA damage sites. In this review, we will focus on the complex interplay between such PTMs, and discuss the importance of their interconnectivity in coding DNA lesions and maintaining the integrity of the genome.

Keywords: DNA repair; Poly(ADP‐ribosyl)ation; SUMO; chromatin; ubiquitin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA Damage*
  • DNA Repair*
  • Gene Expression Regulation*
  • Histones / metabolism*
  • Humans
  • Protein Processing, Post-Translational*
  • Spatio-Temporal Analysis

Substances

  • Chromosomal Proteins, Non-Histone
  • Histones