{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRADX is an RPA-like single-strand DNA binding protein that localizes to replication forks in response to replication stress, where it plays a critical role in maintaining genome stability. By binding to ssDNA via its OB fold domains, RADX not only protects these vulnerable regions from nucleolytic attack but also ensures the proper regulation of RAD51 activity. This regulation is essential because, although RAD51 promotes homology‐directed repair and fork reversal, its excessive binding can lead to replication slowdowns and double‐strand breaks, phenomena that compromise genome integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic studies have revealed that RADX serves as an antagonist to RAD51 at stalled replication forks. It effectively competes with RAD51 for ssDNA binding and directly interacts with the ATP-bound form of RAD51—a process that enhances RAD51’s ATP hydrolysis activity and leads to the destabilization of RAD51 nucleofilaments. This buffering action ensures that an optimal level of RAD51 is maintained to promote fork reversal and protection without triggering nuclease-dependent degradation. In several genetic contexts where key homologous recombination factors such as BRCA1, BRCA2, FANCA, FANCD2, or BOD1L are deficient, inactivation or silencing of RADX restores fork protection, highlighting its pivotal role in modulating RAD51-dependent fork remodeling processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, RADX function is tightly linked to its ability to oligomerize. It acts as a homo-oligomer, and its multimeric state is indispensable for appropriately confining the fork reversal process exclusively to stalled forks. Disruption of RADX oligomerization impairs its regulatory capacity, which underscores the importance of its structural assembly in safeguarding replication fork stability—a feature particularly critical under conditions of replication stress and in cancer cells where RAD51/RADX balance influences sensitivity to chemotherapeutics and PARP inhibitors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Huzefa Dungrawala, Kamakoti P Bhat, Rémy Le Meur, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RADX Promotes Genome Stability and Modulates Chemosensitivity by Regulating RAD51 at Replication Forks."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2017.06.023"}], "href": "https://doi.org/10.1016/j.molcel.2017.06.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28735897"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28735897"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lisa Schubert, Teresa Ho, Saskia Hoffmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RADX interacts with single-stranded DNA to promote replication fork stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embr.201744877"}], "href": "https://doi.org/10.15252/embr.201744877"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29021206"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29021206"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kamakoti P Bhat, Archana Krishnamoorthy, Huzefa Dungrawala, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RADX Modulates RAD51 Activity to Control Replication Fork Protection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2018.06.061"}], "href": "https://doi.org/10.1016/j.celrep.2018.06.061"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30021152"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30021152"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Madison B Adolph, Taha M Mohamed, Swati Balakrishnan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RADX controls RAD51 filament dynamics to regulate replication fork stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2020.12.036"}], "href": "https://doi.org/10.1016/j.molcel.2020.12.036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33453169"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33453169"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Taha Mohamed, Madison B Adolph, David Cortez "}, {"type": "b", "children": [{"type": "t", "text": "Oligomerization of DNA replication regulatory protein RADX is essential to maintain replication fork stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2022.101672"}], "href": "https://doi.org/10.1016/j.jbc.2022.101672"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35120927"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35120927"}]}]}]}