Youri Pavlov

Biography

  Education M.S. Department of Genetics, Leningrad State University, USSR; Genetics Ph.D. Department of Genetics, Leningrad State University, USSR; Genetics

Research Interest

 Our laboratory is interested in the mechanisms of maintenance of genome stability during replication, repair, recombination, transcription and editing.  In particular, we want to understand the mechanisms of global and region-specific control of mutagenesis in different cell types and along chromosomes in eukaryotes.  Evolutionary determined mutation rates depend on levels of endogenous and environmental DNA damage and editing, the efficiency of the repair and high fidelity of chromosomal replication. Impairment of DNA and chromatin metabolism often enhances mutation rates and drastically decreases viability due to cancer onset. Examples are defects in: 8-oxo-dGTPase; proofreading by DNA polymerases Δ and Ε in mice and humans; in mismatch repair in families with hereditary nonpolyposis colorectal cancer; in DNA lesion bypass in XP-V patients in humans. It is also emerges that elevated levels of DNA editing enzymes are mutagenic and can cause cancer. Being deleterious, global mutators cannot account for evolutionary and developmental processes in eukaryotes in the situations when high level of mutagenesis is desired. Current evidence suggests that mutation rates differ significantly along the genome. The most striking example of such variation comes from the immunology field. In specialized cells responsible for antibody production, the variable regions of immunoglobulin genes have six orders of magnitude higher mutation rates than