About this Research Topic
The simultaneous breakage of both strands of DNA, the so-called DNA Double Strand Break (DSB), results in the appearance of broken chromosomes and compromise cell viability. Such DNA lesions are particularly challenging to repair, as they lack an intact DNA strand to use as a template. Indeed, during evolution, several mechanisms that could repair a DSB have arisen. For simplicity, they can be categorized in two broad classes depending on the requirement of a homologous sequence that serves as a template for DNA repair. While all these pathways operate in the same substrate, the DSB itself, the outcome of the repair process can vary enormously. Thus, it is not surprising that a tight regulation between different repair pathways is exerted in cells. Indeed, an unbalance in this regulation might have detrimental consequences, affecting the stability of the genome and, consequently, impacting on the cell or organismal viability and/or fitness.
The signals that determine which DSB repair pathway is used at a given time in a given DNA lesion are still not completely understood. Cellular features, such as cell cycle phase, or local chromatin cues that we are only now starting to understand, play important roles during the choice of the appropriate DNA repair mechanism. In this collection of articles, we aim to expose our current understanding of these local signals that impact the way a DSB is repaired. These include chromatin environment and epigenetic marks, local levels of gene expression, the interference of DNA: RNA hybrids, the presence of atypical DNA conformations close to the breaks or the chemical and physical signatures of the DNA ends themselves. In this Research Topic, we will review how these local cues affect the recognition, signalling and repair of chromosome breaks, how they impact genomic stability, cell viability or organismal fitness and their relationship with human pathologies such as inherited rare diseases, neurodegeneration and cancer.
Keywords: DNA repair, Recombination, NHEJ, Chromatin, Epigenetic marks
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.