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Academic Background

Peterson Lab Web Page

Craig Peterson received his BS from the University of Washington in 1983 and his PhD from the University of California, Los Angeles in 1988. He was a Helen Hay Whitney Foundation postdoctoral fellow from 1988-1991, in the Department of Biochemistry and Biophysics at the University of California, San Francisco. In 1992, he joined the University of Massachusetts Medical School as a faculty member in the Program in Molecular Medicine.

How chromosome structure influences nuclear processes

craig peterson's picture 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.Over the years, our general strategy has been to employ yeast molecular genetics to develop detailed models that describe complex nuclear events that can then be directly tested and expanded by subsequent biophysical and biochemical approaches. Much of our efforts over the past few years have focused on ATP-dependent chromatin remodeling enzymes (e.g. SWI/SNF and INO80) that hydrolyze ~1,000 ATPs per minute to alter chromatin structure and thereby regulate transcription, DNA repair, or replication. Our studies are centered on both the regulation and mechanism of this chromatin "remodeling" reaction. Since most of these enzymes are enormous (>1 MDa), multi-subunit enzymes, we are also interested in understanding how these enzymes are assembled and what roles are played by individual subunits. To address these goals we use a broad spectrum of methodologies, including yeast molecular and classical genetics, modern analytical ultracentrifugation, molecular biology, and traditional biochemistry. Notably, these remodeling enzymes are conserved from yeast to mammals, play key roles in gene expression and the maintenance of genome integrity, and loss of their function leads to various disease states.

In addition to our studies on chromatin remodeling enzymes, we also wish to understand the dynamics of chromatin fibers and how fiber condensation influences DNA repair, transcription, and DNA replication. These projects involve the biochemical reconstitution of defined nucleosomal arrays from recombinant histones and DNA templates that contain head-to-tail repeats of nucleosome positioning sequences. Typically, we perform sedimentation velocity experiments in the analytical ultracentrifuge to investigate how histone modifications (e.g. H4 K16 acetylation), histone variants, or heterochromatin proteins (e.g. HP1, Sir3) influence the folding dynamics of these reconstituted chromatin fibers. These biophysical studies are complemented by powerful biochemical assays where we assess how the structure of a chromatin fiber regulates various steps of DNA double strand break repair or DNA replication.

As we learn more about the dynamics of chromatin fibers and the basic mechanics of DNA repair and DNA replication, we have initiated in vivo studies that probe how these processes are coordinated and regulated within cells. For instance, we have recently, found that a DNA double strand break can induce the re-localization of a chromosomal domain to the nuclear envelope and that this compartmentalization inhibits recombinational repair. Interestingly, localization to the nuclear periphery requires components of the telomerase complex and seems to be due to an attempt to heal the chromosome by formation of a new telomere. Similar types of chromosome healing events may also occur at stalled replication forks. We are currently using a variety of cell biological and molecular genetic approaches to dissect the complex decision-making processes that a cell employs in its attempts to maintain genome integrity.

Figure

Research Figure

Figure Legend

3 dimensional EM reconstruction of the 1.15 MDa yeast SWI/SNF chromatin remodeling complex (image courtesy of C. Woodcock and R. Horowitz). Top two panels show two views of yeast SWI/SNF -- dimensions are 27 nm by 8 nm. Bottom two panels show a theoretical docking of a mononucleosome core particle into the presumptive active site. Note the large cavity that provides a perfect fit for the nucleosome core when it is oriented with the entry/exit strands of DNA facing away from the SWI/SNF surface.

Peterson Lab Web Page
One or more keywords matched the following items that are connected to Peterson, Craig
Item TypeName
Academic Article Recruitment of chromatin remodeling machines.
Academic Article Phosphorylation of linker histones regulates ATP-dependent chromatin remodeling enzymes.
Academic Article Chromatin remodeling enzymes: taming the machines. Third in review series on chromatin dynamics.
Academic Article Rad54p is a chromatin remodeling enzyme required for heteroduplex DNA joint formation with chromatin.
Academic Article A conserved Swi2/Snf2 ATPase motif couples ATP hydrolysis to chromatin remodeling.
Academic Article Promoter targeting and chromatin remodeling by the SWI/SNF complex.
Academic Article ATP-dependent chromatin remodeling: going mobile.
Academic Article The Ino80 chromatin-remodeling enzyme regulates replisome function and stability.
Academic Article The insulator binding protein CTCF positions 20 nucleosomes around its binding sites across the human genome.
Academic Article Recombinational repair within heterochromatin requires ATP-dependent chromatin remodeling.
Academic Article Reconstitution of nucleosomal arrays using recombinant Drosophila ACF and NAP1.
Academic Article Chromatin remodeling: nucleosomes bulging at the seams.
Academic Article Chromatin remodeling by the SWI/SNF complex is essential for transcription mediated by the yeast cell wall integrity MAPK pathway.
Academic Article Structural analysis of the yeast SWI/SNF chromatin remodeling complex.
Academic Article Chromatin and the genome integrity network.
Academic Article A histone acetylation switch regulates H2A.Z deposition by the SWR-C remodeling enzyme.
Academic Article Chromatin remodeling activities act on UV-damaged nucleosomes and modulate DNA damage accessibility to photolyase.
Academic Article Cellular machineries for chromosomal DNA repair.
Academic Article ATP-dependent chromatin remodeling.
Academic Article ATP-dependent and ATP-independent roles for the Rad54 chromatin remodeling enzyme during recombinational repair of a DNA double strand break.
Academic Article Effects of HMGN1 on chromatin structure and SWI/SNF-mediated chromatin remodeling.
Academic Article Histone H4-K16 acetylation controls chromatin structure and protein interactions.
Academic Article Interplay between Ino80 and Swr1 chromatin remodeling enzymes regulates cell cycle checkpoint adaptation in response to DNA damage.
Academic Article DNA translocation and loop formation mechanism of chromatin remodeling by SWI/SNF and RSC.
Academic Article Swi3p controls SWI/SNF assembly and ATP-dependent H2A-H2B displacement.
Academic Article Global regulation of H2A.Z localization by the INO80 chromatin-remodeling enzyme is essential for genome integrity.
Academic Article SWI/SNF- and RSC-catalyzed nucleosome mobilization requires internal DNA loop translocation within nucleosomes.
Academic Article Releasing the brakes on a chromatin-remodeling enzyme.
Concept Chromatin Assembly and Disassembly
Academic Article Chromatin dynamics: flipping the switch on a chromatin remodeling machine.
Academic Article Chromatin dynamics: interplay between remodeling enzymes and histone modifications.
Academic Article Direct interactions promote eviction of the Sir3 heterochromatin protein by the SWI/SNF chromatin remodeling enzyme.
Academic Article Structural analyses of the chromatin remodelling enzymes INO80-C and SWR-C.
Academic Article Response to Comment on "A histone acetylation switch regulates H2A.Z deposition by the SWR-C remodeling enzyme".
Academic Article Genomic Nucleosome Organization Reconstituted with Pure Proteins.
Academic Article Hsp90 and p23 Molecular Chaperones Control Chromatin Architecture by Maintaining the Functional Pool of the RSC Chromatin Remodeler.
Academic Article Nucleosome-like, Single-stranded DNA (ssDNA)-Histone Octamer Complexes and the Implication for DNA Double Strand Break Repair.
Academic Article Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes.
Academic Article Chromatin remodeling: a complex affair.
Academic Article Transient Kinetic Analysis of SWR1C-Catalyzed H2A.Z Deposition Unravels the Impact of Nucleosome Dynamics and the Asymmetry of Histone Exchange.
Academic Article Distinct transcriptional roles for Histone H3-K56 acetylation during the cell cycle in Yeast.
Academic Article Mechanism of Long-Range Chromosome Motion Triggered by Gene Activation.
Academic Article Ruler elements in chromatin remodelers set nucleosome array spacing and phasing.
Academic Article SWI/SNF senses carbon starvation with a pH-sensitive low-complexity sequence.
Academic Article H2A.Z deposition by SWR1C involves multiple ATP-dependent steps.
Academic Article Fluorescence approaches for biochemical analysis of ATP-dependent chromatin remodeling enzymes.
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