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ELUCIDATION OF FACTORS IMPACTING HOMOLOGOUS RECOMBINATION IN MAMMALIAN MEIOSIS

Cherry, Sheila M.

Abstract Details

2007, Doctor of Philosophy, Case Western Reserve University, Genetics.
Meiotic recombination, or crossing-over, maintains associations between homologous chromosomes as they prepare to enter the cellular divisions. If this process is perturbed, meiotic abnormalities ensue. Indeed, in humans an abnormal number or location of recombination events is the only known molecular correlate of aneuploidy (monosomy or trisomy). As such abnormalities are the leading known cause of miscarriages and mental retardation in our species, understanding the link between recombination and chromosome segregation is of great clinical significance. Accordingly, in my thesis research I have utilized both environmental and genetic approaches to understand the way in which crossovers (COs) are positioned in the mammalian genome, and how CO placement affects chromosome segregation. I conducted two sets of studies, analyzing mouse meiosis in each instance. First, the meiotic environment was altered via exposure to a chemotoxin which would introduce additional DNA breaks in early meiotic cells. The results of this study suggest the presence of crossover homeostasis in mammals, a mechanism to maintain the number of crossovers when the number of DSBs is modified. Second, to understand crossover control, the recombination pathway was altered via genetic mutation. Disruptions in the early or late DSB repair processes (Mre11 and Pms2 mutants, respectively) indicated that the fidelity of recombination depends partly on the successful completion of synapsis, and that, as in humans, crossover placement is important for proper chromosome segregation.
Terry Hassold (Advisor)
180 p.

Recommended Citations

Citations

  • Cherry, S. M. (2007). ELUCIDATION OF FACTORS IMPACTING HOMOLOGOUS RECOMBINATION IN MAMMALIAN MEIOSIS [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1154979383

    APA Style (7th edition)

  • Cherry, Sheila. ELUCIDATION OF FACTORS IMPACTING HOMOLOGOUS RECOMBINATION IN MAMMALIAN MEIOSIS. 2007. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1154979383.

    MLA Style (8th edition)

  • Cherry, Sheila. "ELUCIDATION OF FACTORS IMPACTING HOMOLOGOUS RECOMBINATION IN MAMMALIAN MEIOSIS." Doctoral dissertation, Case Western Reserve University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1154979383

    Chicago Manual of Style (17th edition)