Yale Department of Genetics, Faculty, Joann Sweasy

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Joann Sweasy

Associate Professor of Therapeutic Radiology and Genetics and Cancer Genetics Program

* B.A. Beaver College, 1980
* Ph.D. Rutgers, The State University of New Jersey, 1989

Research Interests:

* Genome Stability
* Mutagenesis
* DNA Replication
* DNA Repair
* Carcinogenesis

Other interests:

* Association for Women in Science

Honors:

* Argall and Anna Hull Award
* American Cancer Society Junior Faculty Research Award
* Donaghue Investigator Award

Current Research:

A major goal of the research conducted in my laboratory is to study the relationship between mutations and cancer. Therefore we concentrate our efforts on studying the mechanism of mutagenesis by a DNA polymerase, polymerase § (Pol §). We employ genetic screens to identify amino acid residues of Pol § that function in promoting the fidelity of DNA synthesis. The Pol § mutant proteins identified in these screens are then analyzed using kinetics to determine the mechanism(s) Pol § employs to synthesize DNA accurately. We also study the cellular role of Pol § and have shown that Pol § participates in base excision repair and in the process of meiosis. We are pursuing these studies to determine how Pol § makes errors during base excision repair and to identify the role of Pol § in meiosis.

Pol § IgG stains discrete foci on mouse chromosome homologs during prophase I of meiosis in mouse spermatocytes. Mouse spermatocytes in early prophase. A, B) Nucleus in late zygonema. Pol §-stained nuclei (red) are on the left; Pol § and Cor I-stained nuclei (white) on the right. C) Nucleus in mid-pachynema. Merged image of Pol § and Cor I-stained nucleus. D) Nucleus in late pachynema and proceeding into diplonema. Merged image of Pol § and Cor I-stained nucleus. Control experiments done in parallel with equivalent chromosomal spreads using preimmune serum or Pol §-depleted IgG fractions yielded no detectable staining (data not shown).

Representative Publications:

Washington, S.L., Yoon, M.S., Chagovetz, A.M., Li, S.-X., Clairmont, C., Preston, B.D., Eckert, K.A., Sweasy, J.B. A genetic system to identify DNA polymerase § mutator mutants. Proc. Natl. Acad. Sci. 94: 1321-1326, 1997.

Chagovetz, A.M., Sweasy, J.B., and Preston, B.D. Increased activity and fidelity of DNA polymerase § on single-nucleotide gapped DNA. J. Biol. Chem. 272: 27501-27504, 1997.

Clairmont, C.A. and Sweasy, J.B. The Pol beta-14 dominant negative rat DNA polymerase beta mutator mutant commits errors during the gap-filling step of base excision repair in Saccharomyces cerevisiae. J. Bacteriol. 180: 2292-2297, 1998.

Kosa, J.L. and Sweasy, J.B. 3'-Azido-3'-deoxythymidine-resistant mutants of DNA polymerase beta identified by in vivo selection. J. Biol. Chem. 274: 3851-3858, 1999.

Li, S.-X., Vaccaro, J.A., and Sweasy, J.B. (1999) Involvement of Phenylalanine 272 of DNA Polymerase Beta in Discriminating Between Correct and Incorrect Deoxynucleoside Triphosphates. Biochemistry 38: 4800-4808.

Clairmont, C.A., Narayanan, L, Sun, K.-W., Glazer, P.M., and Sweasy, J.B. (1999) The tyrosine 265 to cysteine mutator mutant of DNA polymerase beta induces a mutator phenotype in mouse LN12 cells. Proc. Natl. Acad. Sci. USA 96: 9580-9585.

Kosa, J.L. and Sweasy, J.B. (1999) The E249K mutator mutant of DNA polymerase § extends mispaired termini. J. Biol. Chem. 274:35866-35872.

Contact Information:

joann.sweasy@yale.edu


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