Reconsidering pathway choice: a sequential model of mammalian DNA double-strand break pathway decisions

DNA double-strand breaks can be repaired through ligation-based pathways (non-homologous end-joining) or replication-based pathways (homologous recombination) in eukaryotic cells. The decisions that govern these outcomes are widely viewed as a competition between factors that recognize DNA ends and...

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Veröffentlicht in:Current opinion in genetics & development 2021-12, Vol.71, p.55-62
1. Verfasser: Paull, Tanya T
Format: Artikel
Sprache:eng
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Zusammenfassung:DNA double-strand breaks can be repaired through ligation-based pathways (non-homologous end-joining) or replication-based pathways (homologous recombination) in eukaryotic cells. The decisions that govern these outcomes are widely viewed as a competition between factors that recognize DNA ends and physically promote association of factors specific to each pathway, commonly known as ‘pathway choice’. Here I review recent results in the literature and propose that this decision is better described as a sequential set of binding and end processing events, with non-homologous end joining as the first decision point. Physical association and co-localization of end resection factors with non-homologous end-joining factors suggests that ends are transferred between these complexes, thus the ultimate outcome is not the result of a competition but is more akin to a relay race that is determined by the efficiency of the initial end-joining event and the availability of activated DNA end-processing enzymes.
ISSN:0959-437X
1879-0380
DOI:10.1016/j.gde.2021.06.011