title: Spatiotemporal regulation of posttranslational modifications in the DNA damage response.
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.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden nico.dantuma@ki.se.
authors.forename: Nico P
authors.initials: NP
authors.lastname: Dantuma
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Haico
authors.initials: H
authors.lastname: van Attikum
mesh_terms: D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D006801:Humans; D011499:Protein Processing, Post-Translational; D062211:Spatio-Temporal Analysis
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D006657:Histones
keywords: DNA repair; Poly(ADP‐ribosyl)ation; SUMO; chromatin; ubiquitin