When a mutation, designated rad51M1, was generated in the mouse MmRAD51 gene,mutant embryos died shortly after implantation. rad51M1 cells exhibitedhypersensitivity to ionizing radiation, reduced proliferation, programmed celldeath and chromosome loss. The disruption of MmRad51 protein-proteininteractions stopped cell proliferation and/or reduced cell viability. Severalproteins that interact with MmRad51 have been identified including, forexample Brca2 and M96. Additionally, Rad51 self-associates via the N-terminalregion. When a single residue was changed from a conserved lysine to analanine, the alteration proved toxic to cells. Moreover, a rad51 allele thatlacked the RecA homology region was also deleterious to cells. In view of theabove, it is clear that inhibiting MmRad51 function or the function of anymolecule that associates with MmRad51, or any molecule in the Rad51 or Rad52pathways, hinders cell proliferation and/or viability. Accordingly, moleculescapable of blocking these critical DNA repair pathways may be effective astherapeutics for inhibiting cell proliferation.
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