Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Patent
1997-11-05
2000-05-02
Ketter, James
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
435196, 530350, 536 232, 536 235, C12Q 168
Patent
active
060571047
ABSTRACT:
When a mutation, designated rad51.sup.M1, was generated in the mouse MmRAD51 gene, mutant embryos died shortly after implantation. rad51.sup.M1 cells exhibited hypersensitivity to ionizing radiation, reduced proliferation, programmed cell death and chromosome loss. The disruption of MmRad51 protein--protein interactions stopped cell proliferation and/or reduced cell viability. Several proteins that interact with MmRad51 have been identified including, for example Brca2 and M96. Additionally, Rad51 self-associates via the N-terminal region. When a single residue was changed from a conserved lysine to an alanine, the alteration proved toxic to cells. Moreover, a rad51 allele that lacked the RecA homology region was also deleterious to cells. In view of the above, it is clear that inhibiting MmRad51 function or the function of any molecule that associates with MmRad51, or any molecule in the Rad51 or Rad52 pathways, hinders cell proliferation and/or viability. Accordingly, molecules capable of blocking these critical DNA repair pathways may be effective as therapeutics for inhibiting cell proliferation.
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Ketter James
Lexicon Genetics Incorporated
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