Document Type
Article
Publication Date
2018
Keywords
fork reversal, fork protection, RAD51, RADX, replication stress, MRE11, BRCA1, Fanconi anemia
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.celrep.2018.06.061
Abstract
RAD51 promotes homologous recombination repair (HR) of double-strand breaks and acts during DNA replication to facilitate fork reversal and protect nascent DNA strands from nuclease digestion. Several additional HR proteins regulate fork protection by promoting RAD51 filament formation. Here, we show that RADX modulates stalled fork protection by antagonizing RAD51. Consequently, silencing RADX restores fork protection in cells deficient for BRCA1, BRCA2, FANCA, FANCD2, or BOD1L. Inactivating RADX prevents both MRE11- and DNA2-dependent fork degradation. Furthermore, RADX overexpression causes fork degradation that is dependent on these nucleases and fork reversal. The amount of RAD51 determines the fate of stalled replication forks, with more RAD51 required for fork protection than fork reversal. Finally, we find that RADX effectively competes with RAD51 for binding to single-stranded DNA, supporting a model in which RADX buffers RAD51 to ensure the right amount of reversal and protection to maintain genome stability.
Rights Information
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Cell Reports, v. 24, issue 3, p. 538-545
Scholar Commons Citation
Bhat, Kamakoti P.; Krishnamoorthy, Archana; Dungrawala, Huzefa; Garcin, Edwige B.; Modesti, Mauro; and Cortez, David, "RADX Modulates RAD51 Activity to Control Replication Fork Protection" (2018). Molecular Biosciences Faculty Publications. 105.
https://digitalcommons.usf.edu/bcm_facpub/105
