Regulation of DSB Repair by Cell-cycle Signaling and the DNA Damage Response

Of the many types of DNA lesions, DNA double-strand breaks (DSBs) are considered the most harmful, because one unrepaired DSB is sufficient to trigger permanent growth arrest and cell death. In addition, DSBs are potent inducers of gross chromosomal rearrangements such as deletions, translocations and amplifications. DSB signalling and repair through different pathways is crucial to preserve genomic integrity and maintain cellular homeostasis. Therefore, it is no wonder if the cell finely regulates DSB repair pathways in the different cell cycle phases and following activation of the DNA damage checkpoint. In this short essay we will illustrate some known aspects of the regulation of DSB repair in the mitotic cell cycle. In particular we will focus on the balance of the two main DSB repair pathways: NHEJ, non-homologous end joining and H(D)R, homologous (directed) recombination, as well as on the regulation of the resolution of joint molecules that arise during H(D)R.