BERing the burden of damage: Pathway crosstalk and posttranslational modification of base excision repair proteins regulate DNA damage management

• Type of Material: Article
• Authors: Kristin Limpose, Emory University; Anita Corbett, Emory University; Paul Doetsch, Emory University
• Language: English
• Date: 2017-08-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Elsevier B.V.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.dnarep.2017.06.007
• Title of Journal or Parent Work: DNA Repair
• ISSN: 1568-7864
• Volume: 56
• Start Page: 51
• End Page: 64
• Grant/Funding Information: Support for this work was provided by NIH grant ESES011163 (PWD), Emory University School of Medicine (PWD), the Winship Cancer Institute of Emory University (PWD), and by NIH grant GM058728 (AHC).
• Keywords: DNA damage; DNA repair hubs; HUMAN 8-OXOGUANINE-DNA GLYCOSYLASE; STRAND-BREAK REPAIR; AP-ENDONUCLEASE APE1/REF-1; Science & Technology; DNA pathway crosstalk; Toxicology; GROUP-B PROTEIN; Post-translational modifications PTMs; MODIFIER SUMO MODIFICATION; CRITICAL LYSINE RESIDUES; COCKAYNE-SYNDROME PATIENTS; Base excision repair BER; CELL NUCLEAR ANTIGEN; CYCLE-DEPENDENT EXPRESSION; Genetics & Heredity; ESTROGEN-RECEPTOR-ALPHA; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Oncology; Biology, General

Abstract

DNA base damage and non-coding apurinic/apyrimidinic (AP) sites are ubiquitous types of damage that must be efficiently repaired to prevent mutations. These damages can occur in both the nuclear and mitochondrial genomes. Base excision repair (BER) is the frontline pathway for identifying and excising damaged DNA bases in both of these cellular compartments. Recent advances demonstrate that BER does not operate as an isolated pathway but rather dynamically interacts with components of other DNA repair pathways to modulate and coordinate BER functions. We define the coordination and interaction between DNA repair pathways as pathway crosstalk. Numerous BER proteins are modified and regulated by post-translational modifications (PTMs), and PTMs could influence pathway crosstalk. Here, we present recent advances on BER/DNA repair pathway crosstalk describing specific examples and also highlight regulation of BER components through PTMs. We have organized and reported functional interactions and documented PTMs for BER proteins into a consolidated summary table. We further propose the concept of DNA repair hubs that coordinate DNA repair pathway crosstalk to identify central protein targets that could play a role in designing future drug targets.