Project: Research project

Grant Details


Ionizing radiation results in the cessation of the initiation of DNA
replication. DNA single and double stranded breaks and DNA-protein
crosslinks are major classes of damage which may contribute to the block of
DNA replication. We propose to study the covalent DNA protein crosslinks
(DPC) which occur after ionizing radiation and discover whether they
represent nuclear structural proteins that could constitute a mechanism
whereby DNA replication is halted. The research plan includes the
biochemical characterization of the protein and DNA involved in the DPC.
The proteins will be analyzed with respect to molecular weight, isoelectric
point, and peptide mapping. The purported nuclear matrix proteins and
chromosomal attachment proteins have been described and will be compared to
the DPC proteins. The DNA will be tested for its size and
heterochromicity. A long-range goal of this study is to produce antibody
directed against the purified protein(s) involved in the DPC. The antibody
or antibodies are important for determining the localization of the DPC
within an intact cell, providing the means to generate a specific probe for
the DPC and contributing to the purification of the proteins and DNA in the
DPC under non-denaturing conditions. The biological features associated
with the DPC production include investigating the metabolic turnover of the
protein(s), and the dependence of the DPC upon protein and RNA synthesis.
Further, AT cells, which do not halt DNA synthesis after ionizing radiation
will be used to test the suggested link between the covalent DPC production
and the initiation of DNA synthesis. These proposed studies will
contribute to the knowledge of DNA-protein crosslinks and may provide a
plausible mechanism whereby DNA replication is halted by ionizing radiation.
Effective start/end date7/1/812/28/89


  • National Institutes of Health


  • Medicine(all)


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