Our laboratory is studying the genetic and biochemical mechanisms of genetic recombination, DNA repair and suppression of spontaneous mutations primarily using Saccharomyces cerevisiae as a model system. Work in S. cerevisiae falls in two interrelated areas - 1) the analysis of the proteins and genes that function in DNA mismatch repair; and 2) elucidation of the pathways that prevent translocations and other types of gross chromosomal rearrangements, and the analysis of the proteins that function in these pathways. The Kolodner lab also has research interests in the area of investigating the genetics of cancer susceptibility and development that follows on previous studies showing that a common cancer susceptibility syndrome, Lynch Syndrome (hereditary non-polyposis colorectal cancer), is due to inherited defects in DNA mismatch repair genes. This work is focused on understanding whether genes that prevent genome instability act as tumor suppressor genes in humans and whether defects in these genes can be therapeutically targeted.
Research Focus Areas:
DNA Replication and Repair | Genetics and Genomics | Biochemistry and Structural Biology | Signal Transduction | Stem Cell Biology
Putnam, CD, Hayes, TK, and Kolodner, RD. Specific pathways prevent duplication-mediated genome rearrangements. Nature. 2009;460:984-989.
Hombauer, H, Campbell, CS, Smith, CE, Desai, A, and Kolodner, RD. Visualization of eukaryotic DNA mismatch repair reveals distinct recognition and repair associated intermediates
. Cell. 2011;147:1040-1053.
Hombauer, H, Srivatsan, A, Putnam, CD, and Kolodner, RD. Mismatch repair, but not heteroduplex rejection, is temporally coupled to DNA replication
. Science. 2011;334:1713-1716.
Putnam, CD, Soltero, S, Martinez, S, Hayes, TK, Chan, J, and Kolodner, RD. Bioinformatic identification of genes suppressing genome instability
. Proc. Natl. Acad. Sci. USA. 2012;109:E3251-3259.
Bowen, N, Smith, CE, Srivatsan, A, Wilcox, SS, Griffith, JD, and Kolodner, RD. Reconstitution of long and short patch mismatch repair reactions using Saccharomyces cerevisiae proteins
. Proc. Natl. Acad. Sci. USA. 2013;110:18472-18477.