Regulation of non-homologous end joining via post-translational modifications of components of the ligation step.

Abstract

DNA double-strand breaks are the most serious type of DNA damage and non-homologous end joining (NHEJ) is an important pathway for their repair. In Saccharomyces cerevisiae, three complexes mediate the canonical NHEJ pathway, Ku (Ku70/Ku80), MRX (Mre11/Rad50/Xrs2) and DNA ligase IV (Dnl4/Lif1). Mammalian NHEJ is more complex, primarily as a consequence of the fact that more factors are involved in the process, and also because higher chromatin organization and more complex regulatory networks exist in mammals. In addition, a stronger interconnection between the NHEJ and DNA damage response (DDR) pathways seems to occur in mammals compared to yeast. DDR employs multiple post-translational modifications (PTMs) of the target proteins and mutual crosstalk among them to ensure highly efficient down-stream effects. Checkpoint-mediated phosphorylation is the best understood PTM that regulates DDR, although recently SUMOylation has also been shown to be involved. Both phosphorylation and SUMOylation affect components of NHEJ. In this review, we discuss a role of these two PTMs in regulation of NHEJ via targeting the components of the ligation step.