Uniformed Services University of the Health Sciences
Department of Biochemistry and Molecular Biology
4301 Jones Bridge Road, C1094
Bethesda, Maryland 20814-4799
Fax: (301) 295-3512
Lab: (301) 295-9417
M.S., Dept of Biology, Moscow State University, Moscow, Russia
Ph.D., Shemyakin & Ovchinnikov Inst. of Bioorganic Chemistry, Moscow, Russia
Aneuploidy - the wrong number of chromosomes in an individual - is the leading cause of birth defects in humans. It results from errors in the segregation of homologous chromosomes (homologs) during gametogenesis. The proper segregation is ensured by meiotic recombination. It begins with the introduction of DNA double stranded breaks followed by their repair using the intact DNA of a homologous chromosome as a template. This leads to a temporal association of the homologs stabilized by crossing-overs. Such an arrangement into pairs ensures the orderly segregation of homologous chromosomes to the opposite poles of dividing nuclei so that each gamete receives one (and only one) homolog of each pair. The homologs that fail to pair segregate randomly, and have a 50% chance to go into the same daughter cell.
An estimated 10 to 30% of fertilized human eggs have the wrong number of chromosomes resulting in at least 5% of conceptions being aneuploid. Most of them abort before term making aneuploidy the leading known cause of pregnancy loss (~35% of miscarriages and ~4% of stillbirths). The number of aneuploid babies approaches 0.3% in newborns and those that survive face devastating consequences including developmental disabilities and mental retardation. Our long-term goal is to elucidate the mechanisms behind faulty meiotic recombination resulting in aneuploidy in mammals.
Both reduced recombination and abnormal location of recombination events are well-documented factors leading to aneuploidy. Therefore our research focuses both on the mechanisms that ensure optimal levels of homologous recombination as well as on the mechanisms that control the distribution of recombination events. We employ a wide range of approaches ranging from the biochemical characterization of purified proteins and the generation of genetically modified mice to the genome-wide characterization of the distribution of recombination events and the analysis of spatial organization of meiotic chromosomes.
Brick K, Smagulova F, Khil P, Camerini-Otero RD, Petukhova GV. Genetic recombination is directed away from functional genomic elements in mice. (2012) Nature, 485(7400): 642-645.
Khil, PP, Smagulova, F, Brick, KM, Camerini-Otero, RD., Petukhova, GV. Sensitive mapping of recombination hotspots using sequencing-based detection of ssDNA. (2012) Genome Res., 22(5): 957-65.
Smagulova F, Gregoretti IV, Brick K, Khil P, Camerini-Otero RD, Petukhova GV. Genome-wide analysis reveals novel molecular features of mouse recombination hotspots. (2011) Nature, 472(7343): 375-378.
Petukhova G., Pezza RJ, Vanevski F, Ploquin M, Masson JY and Camerini-Otero RD. The Hop2 and Mnd1 proteins act in concert with Rad51 and Dmc1 in meiotic recombination (2005) Nat Struct Mol Biol. 12(5), 449-53.
Petukhova G., Romanienko P, and Camerini-Otero RD. The Hop2 Protein has a Direct Role in Promoting Inter-Homolog Interactions during Mouse Meiosis. (2003) Dev. Cell 5(6), 927-936.
Petukhova G., Sung P, Klein H. Promotion of Rad51-dependent D-loop formation by yeast recombination factor Rdh54/Tid1. (2000) Genes Dev. 14(17), 2206-15.
Petukhova G., S.A. Stratton, and P. Sung. Catalysis of Homologous DNA Pairing by Yeast Rad51 and Rad54 Proteins. (1998) Nature, 393:91-94.