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Título: | Strand asymmetry of DNA damage tolerance mechanisms |
Autor: | Cañas, Juan C. CSIC ORCID; Jurado-Santiago, Dolores CSIC; Al Mamun, Mohammed CSIC ORCID; Sacristán, María P. CSIC ORCID CVN ; Morafraile, Esther C.; Zamarreño, Javier; Fujiki, Katsunori; Shirahige, Katsuhiko; Bueno, Avelino CSIC ORCID; Bermejo, Rodrigo CSIC ORCID CVN | Fecha de publicación: | 22-ene-2024 | Editor: | Cold Spring Harbor Laboratory Press | Citación: | BioRxiv (2024) | Resumen: | DNA damage tolerance mechanisms are crucial for timely and accurate chromosomal replication in response to DNA polymerase stalling. Ubiquitylation of the replicative sliding clamp PCNA drives major tolerance pathways, error-free homologous recombination template switching and error-prone translesion synthesis, though their dynamics at forks and pathway choice determinants are poorly understood. Using strand-specific genomics we revealed an asymmetric nature of tolerance pathways, characterized by preferential template switching-driven recombinase engagement of stalled nascent lagging strands and translesion synthesis usage in response to leading strand polymerase stalling. This asymmetry, determined by a strand-dynamic interplay between PCNA-ubiquitin writers and erasers, likely stems from necessities dictated by leading and lagging strand replication mechanisms and has implications for asymmetric mutation inheritance. | Descripción: | 19 p.-4 fig. | Versión del editor: | https://doi.org/10.1101/2024.01.21.576515 | URI: | http://hdl.handle.net/10261/352114 | DOI: | 10.1101/2024.01.21.576515 |
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