The Department of Chemical and Systems Biology Presents

James E. Haber, Ph.D.
Abraham and Etta Goodman Professor of Biology and
Director of the Rosenstiel Basic Medical Sciences Research Center
Brandeis University

“Stability and Instability in Repairing a Broken Chromosome”

Tumor cells are highly efficient in joining broken DNA ends together, but they appear to lack the ability to repair breaks by the more accurate homologous recombination mechanisms; hence an average tumor cell has 100 “structural variants.”  We are interested in the mechanisms that preserve genome integrity, by several homologous recombination mechanisms.  Using budding yeast as a model system we can create site-specific double-strand breaks (DSBs) in a highly synchronous manner, allowing us to monitor the kinetics of repair and to study the proteins required for several related repair mechanisms.  We are interested in how the Rad51 recombination protein accomplishes the search for homologous sequences located elsewhere in the genome and the role that proximity plays in facilitating repair.  Moreover, even accurate repair has its limits, as there is a surprisingly high rate of errors associated with the copying of a homologous template used to patch up the DSB.

Reading Material:

1. Anand R, Beach A, Li K, Haber J. Rad51-mediated double-strand break repair and mismatch correction of divergent substrates. Nature 2017 Apr 20; 544(7650):377-380.doi: 10.1038/nature22046. Epub 2017 Apr 12.
2. Haber, JE.  DNA Repair: The Search for Homology.  Bioessays. 2018 May;40(5):e1700229. doi: 10.1002/bies.201700229. Epub 2018 Mar 30.