Section: Research

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Craig Peterson, Ph.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Program in Molecular Medicine

Joint Faculty In:
   Biochemistry and Molecular Pharmacology

Other Affiliation(s):
   Interdisciplinary Graduate Program

How chromosome structure influences nuclear processes

The overall objective of our research is to determine how chromosome structure influences nuclear processes and to identify and characterize the cellular machines that contend with this structure. Much of our efforts over the past few years have focussed on a genetic and biochemical characterization of an evolutionarily conserved protein complex, yeast SWI/SNF, which hydrolyzes about 1,000 ATPs per minute to make nucleosomal DNA more accessible to the transcription machinery. Our studies are centered on both the regulation and mechanism of this chromatin "remodeling" reaction. To address these goals we use a broad spectrum of methodologies, including yeast molecular and classical genetics, analytical ultracentrifugation, molecular biology, chromosome "painting" (FISH) and spreading, and traditional biochemistry. Although studies on SWI/SNF remain a focus of our research, we have recently expanded our efforts to include studies of mammalian SWI/SNF-like complexes, transcription-associated, nuclear histone acetyltransferases (HATs), as well as nonhistone proteins and histone domains that influence the repressive nature of chromatin.

We are very interested in the roles of chromatin remodeling enzymes (like SWI/SNF and the nuclear HATs) in the control of cell cycle progression. In mammalian cells, the human SWI/SNF complex is a tumor suppressor "gene" that controls the G1/S and S/G2 cell cycle transitions. Recently, we have found that yeast SWI/SNF and the Gcn5p histone acetyltransferase also control the M/G1 cell cycle transition by modulating the expression of genes during late mitosis. These studies have also led to the identification of new components of mitotic chromatin that influence chromosome dynamics, nucleosomal array folding, as well as transcriptional regulation.

In addition to our studies on the control of gene expression, we have initiated a new research focus which investigates how components of the DNA repair machinery deal with the packaging of DNA into nucleosomes. Specifically, we are interested in how DNA double strand breaks are repaired on chromatin substrates in vivo and in vitro. To date we have mapped the sequence of protein-DNA events that occur on a newly formed DNA double strand break in vivo; identified a novel, SWI/SNF-like enzyme, Rad54p, which can use the energy of ATP hydrolysis to facilitate DNA repair of chromatin substrates; and we have identified yeast histone H1 as a key target for ATM-like kinases that initially "sense" the DNA break and transmit the DNA damage signal to the cell cycle and DNA repair machineries. Thus, these new studies further emphasis our global interests in cell cycle control, signal transduction, and chromosome dynamics.

Office: Biotech2 Suite 210
Phone: 508 856 5858
E-mail: Craig.Peterson@umassmed.edu
Keywords: DNA Replication, Biochemistry, Gene Expression

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