
Am J Cancer Res 2012;2(3):249-268
Review Article
Initiation of DNA double strand break repair: signaling and single-stranded 
resection dictates the choice between homologous recombination, 
non-homologous end-joining and alternative end-joining
Anastazja Grabarz*, Aurélia Barascu*, Josée Guirouilh-Barbat, Bernard S Lopez
Université Paris Sud, Laboratoire « Stabilité Génétique et Oncogenèse » CNRS, UMR 8200 and Institut de Cancérologie 
Gustave-Roussy, PR2, 114 Rue Edouard Vaillant, 94805 VILLEJUIF. CNRS, France. *These authors equally contributed to this 
work.
Received April 3, 2012; accepted April 15, 2012; Epub April 21, 2012; Published May 15, 2012
Abstract: A DNA double strand break (DSB) is a highly toxic lesion, which can generate genetic instability and profound genome 
rearrangements. However, DSBs are required to generate diversity during physiological processes such as meiosis or the 
establishment of the immune repertoire. Thus, the precise regulation of a complex network of processes is necessary for the 
maintenance of genomic stability, allowing genetic diversity but protecting against genetic instability and its consequences on 
oncogenesis. Two main strategies are employed for DSB repair: homologous recombination (HR) and non-homologous 
end-joining (NHEJ). HR is initiated by single-stranded DNA (ssDNA) resection and requires sequence homology with an intact 
partner, while NHEJ requires neither resection at initiation nor a homologous partner. Thus, resection is an essential step for 
DSB repair initiation, driving the choice of the DSB repair pathway employed. However, an alternative end-joining (A-EJ) pathway, 
which is highly mutagenic, has recently been described; A-EJ is initiated by ssDNA resection but does not require a homologous 
partner. The choice of the appropriate DSB repair system, for instance according the cell cycle stage, is essential for genome 
stability maintenance. In this context, controlling the initial events of DSB repair is thus an essential step that may be irreversible, 
and the wrong decision should lead to dramatic consequences. Here, we first present the main DSB repair mechanisms and 
then discuss the importance of the choice of the appropriate DSB repair pathway according the cell cycle phase. In a third 
section, we present the early steps of DSB repair i.e., DSB signaling, chromatin remodeling, and the regulation of ssDNA 
resection. In the last part, we discuss the competition between the different DSB repair mechanisms. Finally, we conclude with 
the importance of the fine tuning of this network for genome stability maintenance and for tumor protection in 
fine.(AJCR00000113).
Keywords: DNA double strand break, Homologous recombination, Non homologous end joining, alternative end-joining, 
Resection, chromatin remodeling, genetic instability, genome rearrangements
Address all correspondence to:
Dr. Bernard S Lopez
Université Paris Sud, Laboratoire « Stabilité Génétique et Oncogenèse » CNRS
UMR 8200 and Institut de Cancérologie Gustave-Roussy
PR2, 114 Rue Edouard Vaillant, 94805 VILLEJUIF. CNRS, France.
E-mail: Bernard.Lopez@igr.fr
        
        
          
            
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        American Journal of Cancer Research