Mechanisms of Spontaneous and Induced Deletion
{'Code': '08070100', 'Directorate': {'Abbreviation': 'BIO', 'LongName': 'Direct For Biological Sciences'}, 'Division': {'Abbreviation': 'MCB', 'LongName': 'Div Of Molecular and Cellular Bioscience'}}
{'SignBlockName': 'Philip Harriman', 'PO_EMAI': None, 'PO_PHON': None}
Major genetic rearrangements are at the basis of major biological               processes and constitute a major class of disease related genetic               events.  This proposal is concerned with the origin of deletions,               which are the most extensively studied rearrangements.                          Spontaneous deletions are explained by misalignment mutagenesis                 models, which postulate that during DNA replication single                      stranded regions can undergo slippage followed by interstrand                   mispairing between direct repeats or formation of hairpin                       structures between inverted repeats, but leave open the question                of how these transient intermediates are resolved as deletions                  by enzymes for DNA metabolism.  We know very little about                       deletions induced by mutagens and it is possible that many of                   them are untargeted, i.e. occur at sites not containing mutagenic               lesions.  The overall objective of this proposal is to gain a                   better understanding of the various factors responsible for                     spontaneous and induced deletions.  Specific objectives are: (1)                examine some novel sequences capable of stabilizing deletion                    intermediates, (2) extend earlier observations showing that                     induction of the SOS response can stimulate some deletions, (3)                 determine to what extent mutagen-induced deletions can be                       untargeted as the result of SOS induction, (4) attempt to                       recover deletion intermediates (5) analyze mutations which                      increase deletion frequency in the absence of the recA function.                The experiments proposed are based on the use of preconstructed                 plasmids derived from pBR325 on which deletion of presequenced                  fragments within the EcoR1 site of the CAT (chloramphenicol                     acetyl transferase) gene can be measured as the frequency of Cms-               --Cmr (chloramphenicol sensitive to resistant) revertants, and a                variety of strains carrying mutations in SOS genes.                                                                                                             This is a proposal to study the mechanisms by which genetics                    information is lost from the chromosomes of an organism, either                 spontaneously or as the result of environmental factors (such as                chemicals).  Virtually nothing is known about these mechanisms                  because they have been difficult to study.  The proposed work                   makes use of methods newly developed by the P.I, which should                   shed new light on these mechanisms, Apart from its intrinsic                    scientific interest, loss of genetic information has many                       important medical consequences, among them genetic diseases,                    cancer, and possibly spontaneous abortion and birth defects.
{'FirstName': 'Elias', 'LastName': 'Balbinder', 'PI_MID_INIT': None, 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Elias Balbinder', 'EmailAddress': None, 'NSF_ID': '000321557', 'StartDate': '02/15/1989', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'University of Colorado at Denver', 'CityName': 'AURORA', 'ZipCode': '800452571', 'PhoneNumber': '3037240090', 'StreetAddress': '13001 E 17TH PL STE F428', 'StreetAddress2': None, 'CountryName': 'United States', 'StateName': 'Colorado', 'StateCode': 'CO', 'CONGRESSDISTRICT': '06', 'CONGRESS_DISTRICT_ORG': 'CO06', 'ORG_UEI_NUM': 'MW8JHK6ZYEX8', 'ORG_LGL_BUS_NAME': 'THE REGENTS OF THE UNIVERSITY OF COLORADO', 'ORG_PRNT_UEI_NUM': None}
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{'Code': '111200', 'Text': 'Genetic Mechanisms'}
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1988&All=true', 'xml': '8819144.xml'}