Proteasome-mediated degradation of long-range nucleases negatively regulates resection of DNA double-strand breaks

Autor: Marco Gnugnoli, Carlo Rinaldi, Erika Casari, Paolo Pizzul, Diego Bonetti, Maria Pia Longhese
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: iScience, Vol 27, Iss 7, Pp 110373- (2024)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2024.110373
Popis: Summary: Homologous recombination is initiated by the nucleolytic degradation (resection) of DNA double-strand breaks (DSBs). DSB resection is a two-step process. In the short-range step, the MRX (Mre11-Rad50-Xrs2) complex, together with Sae2, incises the 5′-terminated strand at the DSB end and resects back toward the DNA end. Then, the long-range resection nucleases Exo1 and Dna2 further elongate the resected DNA tracts. We found that mutations lowering proteasome functionality bypass the need for Sae2 in DSB resection. In particular, the dysfunction of the proteasome subunit Rpn11 leads to hyper-resection and increases the levels of both Exo1 and Dna2 to such an extent that it allows the bypass of the requirement for either Exo1 or Dna2, but not for both. These observations, along with the finding that Exo1 and Dna2 are ubiquitylated, indicate a role of the proteasome in restraining DSB resection by negatively controlling the abundance of the long-range resection nucleases.
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