Table of Contents
International Journal of Proteomics
Volume 2011, Article ID 373816, 8 pages
Review Article

Phosphorylation: The Molecular Switch of Double-Strand Break Repair

Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA

Received 15 December 2010; Revised 9 February 2011; Accepted 19 March 2011

Academic Editor: Yaoqi Zhou

Copyright © 2011 K. C. Summers et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Repair of double-stranded breaks (DSBs) is vital to maintaining genomic stability. In mammalian cells, DSBs are resolved in one of the following complex repair pathways: nonhomologous end-joining (NHEJ), homologous recombination (HR), or the inclusive DNA damage response (DDR). These repair pathways rely on factors that utilize reversible phosphorylation of proteins as molecular switches to regulate DNA repair. Many of these molecular switches overlap and play key roles in multiple pathways. For example, the NHEJ pathway and the DDR both utilize DNA-PK phosphorylation, whereas the HR pathway mediates repair with phosphorylation of RPA2, BRCA1, and BRCA2. Also, the DDR pathway utilizes the kinases ATM and ATR, as well as the phosphorylation of H2AX and MDC1. Together, these molecular switches regulate repair of DSBs by aiding in DSB recognition, pathway initiation, recruitment of repair factors, and the maintenance of repair mechanisms.