MD, Medicine, Harvard Medical School, 2008
Dartmouth College
McNair Scholar, 1993
Major: Biology/Environmental Studies
Mentor: John J. Collins, Associate Professor of Biochemistry
Research Topic: The Mechanism of Double Strand Gap Repair in Somatic Cells of Caenorhabditis elegans
The Mechanism of Double Strand Gap Repair in Somatic Cells of Caenorhabditis elegans
The purpose of this research is to study how cells repair double-strand breaks in their chromosomes generated by transposon excision. Specifically, it will determine if the same mechanism operates in somatic cells and germ cells. The nematode, Caenorhabditis elegans, is the system used in this research because it provides ways to monitor these events separately in the germ line and in the soma.
Recent studies in Drosophila (Engels et al., 1990, Cell 62:515-525) provide a model for transposon excision: excision creates a d ouble-strand gap which is repaired with the sister chromatid or the homologous chromosome serving as the template. One important prediction of this model is that reversion of transposon-induced mutations will be elevated dramatically in heterozygous animals because a wild type template is available for double strand gap repair.
Results of this study indicate that this mechanism operates in both the germ line and soma of Drosophila. In C. elegans, germ line excision of the transposon Tc1 has been shown to occur by the same mechanism. In order to determine if the same template-dependent double strand gap repair process operates in the somatic cells of C. elegans., reversion frequencies of a Tc1-induced mutation in somatic cells in homozygous mutants versus heteroallelic animals were compared. Heteroallelic animals containing two mutant unc-54 alleles (one with a deletion in the 3' UTR and the other with a Tc1 insertion at the S' end) were screened for somatic revertants, as detected by their ability to lay eggs. An increase in somatic reversion frequency due to the presence of the heteroallele, similar to that seen in the germ line, would indicate that the mechanism of gap repair in the two cell types is the same. Alternatively, no observed increase in somatic reversion frequency in heteroallelic animals would suggest that the mechanisms of gap repair are different in germ and somatic cells.
Results to date are consistent with the latter possibility: somatic reversion does not appear to be elevated in heterozygous animals. This suggests that a different mechanism for Tc1 excision and double strand gap repair exists in the somatic cells of this organism.
