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Hernan Flores-Rozas, Ph.D.
E-mail:
Research Emphasis:
Mismatch repair (MMR) is the system
that corrects mispaired bases that arise from misincorporation of nucleotides
during DNA replication or as a result of chemical damage to DNA and DNA
precursors. MMR
recognizes mispaired bases present in recombination intermediates and prevents
recombination between divergent DNAs.
The crucial role of MMR proteins in the stabilization of the genome is
illustrated by the finding that inactivation of certain human MMR genes underlie
both inherited cancer susceptibility syndromes and sporadic cancers.
MMR has also been implicated in the cytotoxic response to certain
chemotherapeutic agents and in apoptosis.
The focus of my research is to understand the molecular mechanism of
mismatch repair.
I am interested in how mismatches are recognized and repaired in the
context of DNA replication.
My laboratory uses biochemical and genetic approaches to investigate the
role of replication forks and replication proteins in MMR using the yeast, Saccharomyces
cerevisiae, as a model system.
Selected Publications:
Flores-Rozas, H. and
Kolodner, R. D. (2000) Links between replication, recombination and genome
instability in eukaryotes. Trends Biochem. Science 25, 192-196.
Flores-Rozas, H., Clark, D. D., and Kolodner R.D. (2000) Proliferating cell nuclear antigen and MSH2p-MSH6p interact to form an active mispair recognition complex. Nat Genet. 26, 375-378.
Lau, P. J., Flores-Rozas, H. and Kolodner, R. D. (2002) Isolation and characterization of novel proliferating cell nuclear antigen (POL30) mutants that are specifically defective in DNA mismatch repair. Submitted.