Education:
AB (honors) 1984 Molecular Biology & English (High Honors) - University of California, Berkeley
PhD 1989 Biology - Massachusetts Institute of Technology, Cambridge, Massachusetts
Postdoctoral Research Fellowship:
1989-1993 Oxford University, Oxford, United Kingdom
Started at USC: 2004
Research Topics: Cell Cycle, Growth & Proliferation, DNA Replication, Repair, Modification, DNA & RNA, Cancer Cell Biology
Research Description
Proper replication and faithful segregation of chromosomes are essential to the health of eukaryotic cells. Disruptions in these processes lead to loss of genome stability, growth defects, and cell death, and are associated with cancer and birth defects.
Our work addresses how events of DNA replication are linked to subsequent chromosome remodeling and maintenance of genome integrity. We use fission yeast a model system because of its excellent genetics and superb chromosome biology; all of the genes we study are conserved in humans. Much of our early work addressed the role of the conserved MCM proteins. These related proteins assemble into a hexameric helicase complex required for initiation and elongation stages of DNA replication. We are currently investigating how MCM proteins and associated factors contribute to the maintenance of genome integrity and an intact replication fork. We find that MCMs interact with proteins involved in double strand break repair, suggesting MCMs actively contribute to genome integrity by interacting with recombination machinery.
Several new projects in the lab have begun to examine how chromatin modifications are linked to replication and repair. We cloned two MYST-class histone acetyltransferases, Mst1 and Mst2, which can interact with MCM proteins and with recombination proteins, and we are characterizing their functions. Recently, we showed that the MCM kinase Hsk1, which is essential for replication initiation, is independently required for centromere cohesion in regions of heteromchromatin, again leading us to the question of how replication is linked to assembly of particular chromatin structures. We are also examining these questions in meiosis, a simple developmental pathway for which fission yeast provides an excellent genetic model.
Selected Publications
Gómez E, Nugent R, Laria S, Forsburg SL. - S. pombe histone acetyltransferase Mst1 (KAT5) is an essential protein required for damage response and chromosome segregation. - Genetics [ 2008 ] May 27; . PubMed
Forsburg SL. - The MCM helicase: linking checkpoints to the replication fork. - Biochem Soc Trans [ 2008 ] Feb;36(Pt 1):114-9 . PubMed
Bailis JM, Luche DD, Hunter T, Forsburg SL. - Minichromosome maintenance proteins interact with checkpoint and recombination proteins to promote s-phase genome stability. - Mol Cell Biol [ 2008 ] Mar;28(5):1724-38 . PubMed
Siam R, Gómez EB, Forsburg SL. - Schizosaccharomyces pombe Rad4/Cut5 protein modification and chromatin binding changes in DNA damage. - DNA Cell Biol [ 2007 ] Aug;26(8):565-75 . PubMed
Tabancay AP Jr, Forsburg SL. - Eukaryotic DNA replication in a chromatin context. - Curr Top Dev Biol [ 2006 ] 76:129-84 . PubMed
Forsburg SL, Rhind N. - Basic methods for fission yeast. - Yeast [ 2006 ] Feb;23(3):173-83 . PubMed
Huang HK, Bailis JM, Leverson JD, Gómez EB, Forsburg SL, Hunter T. - Suppressors of Bir1p (Survivin) identify roles for the chromosomal passenger protein Pic1p (INCENP) and the replication initiation factor Psf2p in chromosome segregation. - Mol Cell Biol [ 2005 ] Oct;25(20):9000-15 . PubMed
Gómez EB, Espinosa JM, Forsburg SL. - Schizosaccharomyces pombe mst2+ encodes a MYST family histone acetyltransferase that negatively regulates telomere silencing. - Mol Cell Biol [ 2005 ] Oct;25(20):8887-903 . PubMed
Forsburg SL. - The yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe: models for cell biology research. - Gravit Space Biol Bull [ 2005 ] Jun;18(2):3-9 . PubMed
Pankratz DG, Forsburg SL. - Meiotic S-phase damage activates recombination without checkpoint arrest. - Mol Biol Cell [ 2005 ] Apr;16(4):1651-60 . PubMed
