This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The enzyme Poly (ADP-Ribose) polymerase-1 (PARP1) is a global monitor of chromatin structure and DNA damage repair. PARP1 binds to nucleosomes and poly (ADP-ribosylates) histones and several chromatin-associated factors to expose specific DNA sequences to the cellular machinery involved in gene transcription and/or DNA damage repair. In clinical research, activation of PARP1 in response to DNA damage has recently been implicated as a critical mechanism in those cancers that exhibit chemotherapy-resistance. Nevertheless, the precise interactions between PARP1 and damaged DNA that mediate these critical cellular processes have yet to be determined. We hypothesize that the location, orientation and overall structure of PARP1 when bound to DNA is critical for subsequent activation of the PARP1 enzymatic domain. To answer these critical questions, we have established a collaboration with a research scientist at the NIST center for neutron scattering in order to collect SANS data. Here we propose to collect SAXS data for several PARP1:DNA complexes in various D2O mixtures in order to determine how D20 may affect the samples and to have SAXS data that most precisely matches our SANS data. Taken together data will help us develop a greately improved model of the interactions of PARP1 with damaged DNA and may lead to improved method for inhibiting PARP1 in cancer patients.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001209-32
Application #
8362366
Study Section
Special Emphasis Panel (ZRG1-BCMB-P (40))
Project Start
2011-03-01
Project End
2012-02-29
Budget Start
2011-03-01
Budget End
2012-02-29
Support Year
32
Fiscal Year
2011
Total Cost
$810
Indirect Cost
Name
Stanford University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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