Section: Research

Sharon Cantor, Ph.D.

Academic Role: Assistant Professor

Faculty Appointment(s) In:
   Cancer Biology

Other Affiliation(s):
   Graduate School of Biomedical Sciences

Hereditary Breast Cancer

Breast cancer is the most common hereditary cancer syndrome in the United States. Two genes are associated with hereditary cancer, BRCA1 and BRCA2.  Mutations in these genes predispose women to early onset breast and ovarian cancer.  While human genetics makes it clear that these genes function as tumor suppressors, it is still unclear how these proteins function.  My research efforts have focused on gaining mechanistic insights into the BRCA1-mediated DNA repair and tumor suppression.  We found that the ability of BRCA1 to effectively mediate repair of DNA damage depends on the ability of BRCA1 to directly associate with a novel protein we identified and called BACH1 (BRCA1 Associated C-terminal Helicase).  BACH1 is an enzyme that can unwind the strands of DNA in an energy-dependent reaction. This activity is critical for its role in DNA repair.  Human genetic studies resulted in the identification of two early-onset breast cancer patients with germline sequence changes in the BACH1 coding region.  When these sequence changes were studied in vitro, we found that both mutations resulted in defective BACH1 proteins unable to effectively function as DNA helicases.  This data provides a biochemical link to human disease-predisposing mutations in BACH1 and suggest that BACH1 helicase activity is critical for biological function.  We are actively pursuing these studies on BACH1 in order to more clearly define its biological role in normal cell physiology and ultimately determine why mutations in BACH1 and BRCA1 lead to breast and ovarian cancers.  One major question stemming from this work is whether of BACH1 is a "breast cancer helicase", in particular:

1. Is BACH1 helicase activity regulated by DNA damage or by BRCA1 binding?
2. Is BACH1 binding to BRCA1 required for BACH1 localization in nuclear foci?
3. Are BACH1 null cells more DNA damage sensitive, tumorigenic?
4. Does BACH1 associate with other breast cancer-associated proteins in addition to BRCA1?
5. Is BACH1 activity or expression modified in breast tumors compared to normal tissues?
6. Can we identify other cancer-associated helicases?
   

Office: LRB 415
Phone: 508-856-4421
E-mail: Sharon.Cantor@umassmed.edu
Keywords: Cancer Biology, Cancer, DNA Damage and Repair, DNA Recombination

More on Sharon Cantor's Research Research | Figures | Publications View All Sections on One Page