The Molecular Basis of the Response to Radiation

Abstract

In the third year of this CDA Award we have continued to make progress towards all three Technical Objectives. The most challenging problem is the isolation of novel cDNAs encoding human homologs of yeast DNA damage response genes. Major efforts to isolate cDNAs for RAD9 and DUN1 during the previous year have not been successful. In contrast, two hybrid screens have resulted in the isolation of human homologs of RADl8 and RAD2l. Thus, the focus over year 3 has been the characterization of the human Rad2l protein in mammalian cells. We found alterations in expression of human Rad2l mRNA and protein in human breast cancer cell lines. This has lead to development of immunohistochemistry techniques to now expand this research to human breast cancer samples. In Technical Objective 3 we did not see alteration in RAD21 mRNA or Rad2 I protein phosphorylation in human cells exposed to DNA damage. However, we found that induction of the apoptotic pathway (as opposed to DNA damage itself) induces specific cleavage of the human RAD21 cohesin protein. This cleavage product may play a role in signalling subsequent events in apoptosis or result in aneuploidy in cells that survive the apoptotic response.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2000
Accession Number
ADA387637

Entities

People

  • Sharon Plon

Organizations

  • Baylor College of Medicine

Tags

DTIC Thesaurus Topics

  • Apoptosis
  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Chromosome Aberrations
  • Eukaryotes
  • Fungi
  • Immunohistochemistry
  • Ionizing Radiation
  • Lymphocytes
  • Materials
  • Neoplasms
  • Phosphorylation
  • Proteins
  • Radiation

Fields of Study

  • Biology

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Molecular Genetics
  • Oncology and Biomarker-Based Cancer Detection.