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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/190111
RAD51 is a druggable target that sustains replication fork progression upon DNA replication stress.
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Solving the problems that replication forks encounter when synthesizing DNA is essential to prevent genomic instability. Besides their role in DNA repair in the G2 phase, several homologous recombination proteins, specifically RAD51, have prominent roles in the S phase. Using different cellular models, RAD51 has been shown not only to be present at ongoing and arrested replication forks but also to be involved in nascent DNA protection and replication fork restart. Through pharmacological inhibition, here we study the specific role of RAD51 in the S phase. RAD51 inhibition in non-transformed cell lines did not have a significant effect on replication fork progression under non-perturbed conditions, but when the same cells were subjected to replication stress, RAD51 became necessary to maintain replication fork progression. Notably, the inhibition or depletion of RAD51 did not compromise fork integrity when subjected to hydroxyurea treatment. RAD51 inhibition also did not decrease the ability to restart, but rather compromised fork progression during reinitiation. In agreement with the presence of basal replication stress in human colorectal cancer cells, RAD51 inhibition reduced replication fork speed in these cells and increased γH2Ax foci under control conditions. These alterations could have resulted from the reduced association of DNA polymerase α to chromatin, as observed when inhibiting RAD51. It may be possible to exploit the differential dependence of non-transformed cells versus colorectal cancer cells on RAD51 activity under basal conditions to design new therapies that specifically target cancer cells
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FEU I COLL, Sònia, UNZUETA PAYERAS, Fernando, ERCILLA EGUIARTE, Amaia, PÉREZ-VENTEO, Alejandro, JAUMOT I PIJOAN, Montserrat, AGELL I JANÉ, Neus. RAD51 is a druggable target that sustains replication fork progression upon DNA replication stress.. _PLoS One_. 2022. Vol. 17, núm. 8, pàgs. e0266645. [consulta: 26 de gener de 2026]. ISSN: 1932-6203. [Disponible a: https://hdl.handle.net/2445/190111]