Serrano-Benítez, AlmudenaCortes-Ledesma, FelipeRuiz, Jose F2024-10-282024-10-282020-01-10Front Mol Biosci . 2020 Jan 10:6:153.https://hdl.handle.net/20.500.12105/25324Work in the FC-L laboratory was funded with grants from the Spanish and Andalusian Government (SAF2017-89619-R, CVI-7948, European Regional Development Fund), and the European Research Council (ERC-CoG-2014-647359); and with an individual fellowship for AS-B (Beca Predoctoral AEFAT, Asociacion Espanola Familia Ataxia Telangiectasia). CABIMER was supported by the Andalusian Government.Endogenously-arising DNA double-strand breaks (DSBs) rarely harbor canonical 5'-phosphate, 3'-hydroxyl moieties at the ends, which are, regardless of the pathway used, ultimately required for their repair. Cells are therefore endowed with a wide variety of enzymes that can deal with these chemical and structural variations and guarantee the formation of ligatable termini. An important distinction is whether the ends are directly "unblocked" by specific enzymatic activities without affecting the integrity of the DNA molecule and its sequence, or whether they are "processed" by unspecific nucleases that remove nucleotides from the termini. DNA end structure and configuration, therefore, shape the repair process, its requirements, and, importantly, its final outcome. Thus, the molecular mechanisms that coordinate and integrate the cellular response to blocked DSBs, although still largely unexplored, can be particularly relevant for maintaining genome integrity and avoiding malignant transformation and cancer.engVoRhttp://creativecommons.org/licenses/by/4.0/ATMDNA double strand break (DSB)DNA-PK catalytic subunitNon-homologous DNA end joininggenome instabilityAttribution 4.0 International31998749106153Front Mol Biosciopen access