Double-Strand Break Repair in Repetitive DNA Regions

Abstract

Every day, our cells are exposed to endogenous and exogenous sources of damage which cause double-strand breaks (DSBs). If left unrepaired or misrepaired, DBSs can be highly toxic for the cell resulting in cell death, mutations, or genomic instability, which is a hallmark of cancer development. To deal with such breaks, the cell activates the DNA damage response which will sense the DSB and activate the appropriate repair pathway. Two main repair pathways exist: non-homologous end-joining and homologous recombination. The choice of repair pathway is dependent on different factors such as the cell cycle phase and the chromatin context in which the break occurred. Moreover, the different chromatin organizations will recruit different repair proteins and lead to different repair mechanisms as a way of safeguarding genomic stability. However, in highly repetitive regions of the DNA, such as in constitutive heterochromatin, ribosomal DNA, and centromeres, there are higher risks of aberrant recombination and chromosomal rearrangement occurring during repair due to their repetitive nature. Even though these repetitive regions pose a particular danger to our genome integrity, repetitive elements cover half of our genome. It is therefore essential that the cell ensures proper repair in repetitive DNA regions to maintain genomic integrity. In this review, we give an overview of the current knowledge of the different ways repetitive DNA regions are repaired after DSBs specifically in heterochromatin, ribosomal DNA, and centromeres.