A major source of double strand breaks (DSB) arises during attempted replication across a damaged or nicked DNA template. Replication-related DSBs are thought to be repaired preferentially by homologous recombination, using the intact neighboring sister chromatid as a template for error-free repair. Defective control of sister chromatid recombination (SCR) may allow DSBs to be repaired by error-prone pathways, leading to chromosome instability and cancer. Consistent with this notion, several tumor suppressor genes – BRCA1, BRCA2, the Bloom’s Syndrome gene (BLM), Fanconi Anemia genes (FA) and histone H2AX – have been implicated in SCR. A major focus of this laboratory is to understand how these genes control SCR and to relate this to their tumor suppressor functions. Our long-term goal is to apply this knowledge for prevention and therapy of human cancers.
Scully, R and Livingston, DM. In Search of the tumour suppressor functions of BRCA1 and BRCA2. Nature 2000; 408: 429-432.
Xie A, Puget N, Shim I, Odate S, Jarzyna I, Bassing CH, Alt FW and Scully R. Control of sister chromatid recombination by histone H2AX. Mol Cell 2004; 16: 1017-1025.
Puget N, Knowlton M and Scully R. Molecular analysis of sister chromatid recombination in mammalian cells. DNA Repair 2005; 4: 149-161.
Scully R and Xie A. In my end is my beginning: control of DNA end resection and DSBR pathway “choice” by cyclin-dependent kinases. Oncogene 2005; 24: 2871-6.
Nagaraju G, Odate S, Xie A and Scully R. Differential regulation of short- and long-tract gene conversion between sister chromatids by Rad51C. Mol Cell Biol 2006; 26(21): 8075-8086
External Recognition:
AWARDS:
1997 Dana-Farber Cancer Institute, Richard A. Smith Prize for
Outstanding Research (First Prize).
1999 National Cancer Institute, Howard Temin Award K01 CA79576 (PI)
2002 National Cancer Institute, R01 CA95175 (PI).
2002 Pew Scolars Award (PI).
2002 American Cancer Society Research Scholar Grant (declined)
2004 American Cancer Society Research Scholar Grant, RSG-04-198-01-MGO (PI)
2005 Leukemia and Lymphoma Society Research Scholar Award, 1483-06 (PI)
2007 Award from Milo Gladstein Research Foundation for Bloom's Syndrome
PRESENTATIONS
1996 Invited speaker, National Action Plan on Breast Cancer: “Studies on the BRCA1 Protein”
1997 Invited speaker, AACR meeting, Keystone, CO: “Functional Analysis of BRCA1”
Invited speaker, Breakthrough Breast Cancer, Cambridge, UK: “Interaction of BRCA1 with Rad51”
1998 Keynote lecture, Eurocancer, Paris, France: “Insights into the Function of BRCA1 and BRCA2”
Invited speaker, Gordon Research Conference on DNA Alteration in Transformed Cells, NH: “Role of BRCA1 in Genome Integrity Maintenance”
1999 Invited speaker, Gordon Research Conference on Mammalian DNA Repair, Ventura, CA: “DNA Repair Functions of BRCA1”
Invited speaker and Co-chair, American Society of Clinical Oncology: BRCA1 and BRCA2 Mutations: Insights into Mechanism
Invited speaker, Cambridge, UK: “BRCA1 and BRCA2 Operate on a Common DNA Damage Response Pathway”
Invited speaker, Wayne State University, NIEHS Center for Molecular and Cellular Toxicology: “DNA Repair Functions of BRCA1”
2000 Invited speaker, Gordon Research Conference on Cancer Genetics and Epigenetics, Ventura CA: “Analysis of Function of BRCA1 and BRCA2”
Invited speaker, Physicians and Surgeons Biomedical Sciences Symposium, Arden House, NY: “Functional Analysis of BRCA1”
Invited speaker, Stohlman Symposium, Leukemia and Lymphoma Society: “Mechanisms of Genome Integrity Maintenance: Role of BRCA1”
Invited speaker, American Society for Therapeutic Radiology and Oncology: “Management of Breast Cancer in the Patient with BRCA1/2 Germline Mutations”
2001 Invited speaker and session chair, National Cancer Institute: “BRCA1: Function in Cell Growth and Tumorigenesis”
Invited lecture, Beth Israel Deaconess Medical Center Research Day: “Functional Analysis of BRCA1 in the DNA Damage Response”
2002 Invited lecture, Netherlands Cancer Institute: “Functional Analysis of BRCA1”
Invited lecture, Institut Gustave-Roussy: “Analysis of BRCA1 Recombination Functions”
Invited speaker, EMBO Workshop on Genetic Recombination: “Studies on recombination between sister chromatids”
Invited speker, American Society for Photobiology: “Recombination Functions of BRCA1”
2003 Vice Chair, Gordon Research Conference on Cancer Genetics and Epigenetics, Ventura, CA
2004 Invited speaker, Institute Juan March, workshop on Molecular Cross Talk among Chromosome Fragility Syndromes: “Molecular analysis of sister chromatid recombination in
mammaliam cells”
Invited speaker, Radiation Oncology Research and the DNA Damage Response, Boston, MA: “Recombination functions of BRCA1”
2005 Chair, Gordon Research Conference: “Cancer Genetics and Epigenetics”, Ventura, CA.
Invited speaker, Gordon Research Conference on Mammary Gland Biology, Newport, RI: “Recombination functions of BRCA1 and H2AX”
2006 Planning committee, Pew Scholars Program in the Biomedical Sciences Annual meeting.
Invited speaker, Pew Annual meeting: “Sister chromatid recombination and cancer”
2007 Invited speaker, Gordon Research Conference on Cancer Genetics and Epigenetics.
Invited Speaker, Keystone Conference on Epigenetics: Regulation of Chromatin Structure in Development and Disease.
COMMITTEE ASSIGNMENTS
1999- Breast Cancer Research: Editorial Board
2001- Cancer Biology and Therapy: Editorial Board
2003 Vice Chair, Gordon Research Conference on Cancer Genetics and Epigenetics
2005 Chair, Gordon Research Conference on Cancer Genetics and Epigenetics
Major Collaborative Activities:
Ongoing collaboration with Fred Alt (HHMI/Childrens' Hospital) on functional analysis of H2AX.
Ongoing collaborations to use functional genomics to identify new genes that regulate homologous recombination in mammalian cells.
