Molecular Contacts and Their Role in DNA Replication
{'Code': '08070400', 'Directorate': {'Abbreviation': 'BIO', 'LongName': 'Direct For Biological Sciences'}, 'Division': {'Abbreviation': 'MCB', 'LongName': 'Div Of Molecular and Cellular Bioscience'}}
{'SignBlockName': 'Marcia Steinberg', 'PO_EMAI': None, 'PO_PHON': None}
The long range goal of the proposal is to elucidate the                         molecular mechanisms whereby the proteins involved in DNA                       replication interact with nucleic acids and precursors of                       nucleic acids.  The specific objective is to study these                        interactions in DNA polymerase I of Escherichia coli using a                    newly developed laser cross-linkin methodology.  The laser                      cross-linking technique allows molecular contacts between                       proteins and DNA to be "frozen" by the formation of a                           covalent bond.  Bond formation is induced by a rapid (8                         nanosecond) pulse from the ultraviolet region of the                            spectrum.  The brevity of bond induction effectively                            "freezes" the equilibrium between proteins and nucleic acids.                   The laser cross-linking technique will be used to define                        contacts and affinities between the various substrate binding                   sites of DNA polymerase I and the substrates themselves.                        Defining these contacts and affinities in parallel with                         studies of kinetic parameters (processivity, synthesis rate,                    exonuclease rates, etc.) should greatly aid our understanding                   of how the polymerase works in its various modes (working                       "forward" as a polymerase and 5' to 3' exonuclease or working                   "backward" as a 3' to 5' exonuclease) and how the "forward"                     and "backward" reactions are regulated with respect to each                     other.  Additionally, there exist a number of mutations in                      DNA polymerase I that alter its function.  These mutant                         proteins will be examined to determine how the altered                          function is related to structural interactions.                                 After defining how multiple catalytic activities are                            coordinated in a single polypeptide, the studies will be                        extended to more complex systems where more than one protein                    is required for assembly and/or function of a DNA replication                   complex.  An understanding of DNA replication may give us an                    indication of where normal systems go awry in cancer and                        various genetic disorders.  The information gleaned from                        defining specific contacts may be useful in designing drugs                     that prevent or control certain disease conditions.
{'FirstName': 'Joel', 'LastName': 'Hockensmith', 'PI_MID_INIT': 'W', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Joel W Hockensmith', 'EmailAddress': None, 'NSF_ID': '000218120', 'StartDate': '09/01/1987', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'University of Virginia Main Campus', 'CityName': 'CHARLOTTESVILLE', 'ZipCode': '229034833', 'PhoneNumber': '4349244270', 'StreetAddress': '1001 EMMET ST N', 'StreetAddress2': None, 'CountryName': 'United States', 'StateName': 'Virginia', 'StateCode': 'VA', 'CONGRESSDISTRICT': '05', 'CONGRESS_DISTRICT_ORG': 'VA05', 'ORG_UEI_NUM': 'JJG6HU8PA4S5', 'ORG_LGL_BUS_NAME': 'RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA', 'ORG_PRNT_UEI_NUM': None}
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[{'Code': '1144', 'Text': 'Molecular Biophysics'}, {'Code': '9120', 'Text': 'CROSS-DIRECTORATE PROGRAMS'}]
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1987&All=true', 'xml': '8704154.xml'}