Between Dec 19, 2024 and Jan 2, 2025, datasets can be submitted to DRUM but will not be processed until after the break. Staff will not be available to answer email during this period, and will not be able to provide DOIs until after Jan 2. If you are in need of a DOI during this period, consider Dryad or OpenICPSR. Submission responses to the UDC may also be delayed during this time.

Browsing by Subject "Meiosis"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Minisatellites in meiosis: crossover regulation and stability of repetitive DNA.
    (2012-04) LeClere, Andrea Ruth
    The minisatellite associated with the human HRAS1 proto-oncogene has an enhancer effect on HRAS1 expression. Rare minisatellite alleles have stronger enhancer activity and are frequently found in primary tumors of cancer patients. Rare alleles derive from a common allele that has undergone an alteration in length; alterations occur primarily during the process of meiotic recombination. Identifying factors that regulate minisatellite stability during meiosis is important to our understanding of the initiation and predisposition of minisatellite-associated human diseases. This is the focus of the Kirkpatrick lab using a minisatellite model system in yeast Saccharomyces cerevisiae where an HRAS1 minisatellite allele has been inserted into the promoter region upstream of the HIS4 locus on chromosome III. In this study, we identified CSM3, TOF1, and MRC1 as factors that contribute to meiotic minisatellite alterations. We also uncovered a novel recombination phenotype associated with the HRAS1 minisatellite in MSH4 and MSH5 mutants. Both of these projects have broader implications on our understanding of factors that regulate minisatellite alterations during meiosis. We present models based on our data and previously published research to explain the observed phenotypes.
  • Thumbnail Image
    Item
    On the genetic control of oocyte meiotic maturation in Caenorhabditis elegans
    (2013-05) Kim, Seongseop
    In sexually reproducing animals, oocytes arrest at diplotene or diakinesis and resume meiosis (meiotic maturation) in response to hormones. Chromosome segregation errors in female meiosis I are the leading cause of human birth defects, and age-related changes in the hormonal environment of the ovary are a suggested cause. Caenorhabditis elegans is emerging as a genetic system for studying hormonal control of meiotic maturation. The meiotic maturation processes in C. elegans and mammals share a number of biological and molecular similarities. Major sperm protein (MSP) and luteinizing hormone (LH), though unrelated in sequence, both trigger meiotic resumption using somatic Gαadenylate cyclase pathways and soma-germline gap-junctional communication. I used C. elegans as a model for studying the genetic control of oocyte meiotic maturation. I conducted a forward genetic screen to identify new regulators of meiotic maturation that function downstream of somatic Gαadenylate cyclase signaling. I screened for mutations that suppress the meiotic maturation defect caused by defective Gαadenylate cyclase signaling and identified ten Sacy of underline acy underline-4 sterility) genetic loci, including sacy-1, which encodes a highly conserved DEAD-box helicase. SACY-1 appears to be a multifunctional protein that establishes a mechanistic link connecting the somatic control of meiotic maturation to germline sex determination, gamete maintenance, and post-transcriptional gene regulation in the germ line. To identify the molecular mechanisms by which sacy-1 functions in multiple germline developmental pathways, I conducted a genome-wide RNAi screen for genetic loci that enhance a hypomorphic sacy-1 mutant allele upon their depletion. This RNAi enhancer screen revealed multiple spliceosomal C complex proteins as genetic interactors of sacy-1. This result suggests several potential models for future work. One possibility is that sacy-1 might function as a spliceosomal component to regulate specific splicing events needed for execution of multiple germline developmental events. Alternatively, sacy-1, together with a subset of spliceosomal C complex components, might regulate downstream protein-RNA transactions important for germline development. While my work provides insights gained from a genetic analysis of meiotic maturation signaling in C. elegans, the conserved factors identified here might inform analysis in other systems through either homology or analogy.