MEIOTIC CROSSOVER PATTERNING IN THE ABSENCE OF ATR Public Deposited

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  • March 20, 2019
Creator
  • Brady, Morgan
    • Affiliation: School of Medicine, Curriculum in Genetics and Molecular Biology
Abstract
  • Meiotic crossovers must be properly patterned to ensure accurate disjunction of homologous chromosomes during meiosis I. Disruption of the spatial distribution of crossovers can lead to nondisjunction, aneuploidy, gamete dysfunction, miscarriage, or birth defects. One of the earliest identified genes involved proper crossover patterning is mei-41, which encodes the Drosophila ortholog of the checkpoint kinase ATR. Although analysis of hypomorphic mutants suggested the existence of crossover patterning defects, it has not been possible to assess patterning in mei-41 null mutants due to maternal-effect embryonic lethality. To overcome this lethality, we constructed mei-41 null mutants in which we expressed wild-type Mei-41 in the germline after completion of meiotic recombination, allowing embryos to survive. We find that crossovers are decreased to about one third of wild-type levels, but the reduction is not uniform, being less severe in the proximal regions of 2L than in distal 2L or on the X chromosome. None of the crossovers formed in the absence of Mei-41 require Mei-9, the presumptive meiotic resolvase, suggesting that Mei-41 functions everywhere along the arm, despite the differential effects of crossover frequency. Interference appears to be significantly reduced or absent in mei-41 mutants, but the reduction in crossover density in centromere-proximal regions is largely intact. We propose that crossover patterning is achieved in a stepwise manner, with suppression related to proximity to the centromere happening prior to crossover designation and interference. In this model, Mei-41 is essential after the centromere effect is established but before crossover designation and interference occur.
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Rights statement
  • In Copyright
Advisor
  • Conlon, Frank
  • Jarstfer, Michael
  • McKay, Daniel
  • Ramsden, Dale
  • Sekelsky, Jeff
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2017
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