The Molecular Basis of the Response to Radiation
Annual rept. 26 May 1999-25 May 2000
BAYLOR COLL OF MEDICINE HOUSTON TX
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In the second year of this three year IDEA 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 year 1 and year 2 have not been successful. In contrast, two hybrid screens have resulted in the isolation of human homologs of RAD18 and RAD21. Thus, the focus over year 2 has been the characterization of the human Rad21 protein in mammalian cells. We found alterations in expression of human Rad21 mRNA and protein in human breast cancer cell lines. This has led 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 Rad21 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 signaling subsequent events in apoptosis or result in aneuploidy in cells that survive the apoptotic response.
- Medicine and Medical Research