New insights into the DNA repair pathway choice with NuA4/TIP60

DNA Repair (Amst). 2022 May:113:103315. doi: 10.1016/j.dnarep.2022.103315. Epub 2022 Mar 3.

Abstract

In eukaryotic cells, DNA double-strand breaks (DSBs) can be repaired through two main pathways, non-homologous end-joining (NHEJ) or homologous recombination (HR). The selection of the repair pathway choice is governed by an antagonistic relationship between repair factors specific to each pathway, in a cell cycle-dependent manner. The molecular mechanisms of this decision implicate post-translational modifications of chromatin surrounding the break. Here, we discuss the recent advances regarding the function of the NuA4/TIP60 histone acetyltransferase/chromatin remodeling complex during DSBs repair. In particular, we emphasise the contribution of NuA4/TIP60 in repair pathway choice, in collaboration with the SAGA acetyltransferase complex, and how they regulate chromatin dynamics, modify non-histone substrates to allow DNA end resection and recombination.

Keywords: Chromatin remodeling; Double-strand break; Histone modifications; NuA4; SAGA; TIP60.