Project: Research project

Project Details


DESCRIPTION: The goal of the research described in this proposal is to
contribute to our understanding of breast cancer by characterizing the
basic functional mechanism of the BRCA2 breast cancer susceptibility
gene. The BRCA2 breast cancer susceptibility gene is thought to
function as a transcription factor and may also play a role in DNA
repair, as suggested by the interaction between BRCA2 and Rad51. The
applicant proposes to characterize the interaction between the BRCA2,
p21 and p53 tumor suppressors. The p21 cell cycle inhibitor and p53
have been implicated in many of the growth regulatory pathways of the
cell, including cell cycle control and DNA repair. His hypothesis is
that BRCA is also intimately involved in these cellular pathways as a
G1/S checkpoint control molecule through its ability to induce p21
expression in a p53 dependent and independent manner. BRCA2 induction
of p21 may (i) inhibit the cell cycle and slow cell growth, and (ii)
pause the cell cycle and DNA replication in response to DNA damage to
allow DNA repair to take place.

The domains of BRCA2 and p53 required to induce p21 will be mapped, as
will the BRCA2 response element of the p21 promoter. The interaction
will then be studied by reconstitution experiments to define its role
in cell growth regulation, cell cycle control, and response to DNA
damage. Little is known about control of the cell cycle and DNA repair
in mammalian systems, and it is possible that BRCA2 is the key to
characterization of these systems. If we can clearly define even one
of the mechanisms of action of BRCA2, in this case the BRCA2/p21/p53
interaction, then this understanding should translate into the
development of genetic and pharmacological intervention for breast and
other cancers.
Effective start/end date8/1/987/31/04


  • Medicine(all)