Our Science – Strathern Website
Jeffrey N. Strathern, Ph.D.
Two general areas of research are pursued in our section: mechanisms of genetic recombination and mechanisms of gene regulation. We are focused on the area of genetic recombination in general and double-strand-break repair in particular. We demonstrated that the DNA synthesis associated with genetic recombination has substantially lower fidelity than that found in general cell duplication. At least two different DNA polymerases have roles in this elevated mutation rate: Base substitutions reverting a non-sense allele are dependent on the translesion polymerase, Pol zeta, encoded by REV3, whereas reversion of frameshift alleles is REV3 independent. We continue to investigate the mechanism of double-strand-break repair and the proteins involved in controlling the fidelity of DNA synthesis during this process. We extended this research to demonstrate meiotic recombination is also mutagenic. DNA palindromes are thought to be a common mechanism of gene amplification found in tumor cells. However, palindromes are particularly difficult to investigate because they are difficult to clone and difficult to sequence. We created yeast strains that tolerate DNA palindromes and developed system in which they can be generated. We also developed a method to sequence DNA palindromes. We are applying these tools to the characterization of DNA palindromes isolated from human tumor cell lines.
We also study the fidelity of transcription. Again, a historically difficult problem for which we developed a genetic screen to identify mutants with reduced fidelity. We have isolated mutations that reduce the fidelity of transcription and have identified mutations in several subunits of RNA polymerase that result in error prone transcription. We are now studying the consequences of increased transcription error rates.
Our collaborators are Stephen Hughes, Michael Kashlev and Ding Jin, NIH.
This page was last updated on 6/7/2013.