Meiotic recombination is required to align homologous chromosomes for segregation during the first meiotic division. Meiocytes monitor key steps in meiosis and defective progression results in activation of meiotic checkpoints that induce programmed cell death. Recent studies have identified elements that control programmed cell death in the germline during the course of normal development as well as in response to cytotoxic injury. But less is known about the genetic control of apoptosis in response to errors in meiotic chromosome metabolism. Preliminary work suggests that meiocytes have both DMA damage-dependent and -independent meiotic checkpoints. Intriguingly, these checkpoints are differentially utilized during spermatogenesis and oogenesis. The work detailed in this proposal seeks to answer these specific aims: 1) to determine which apoptotic signaling cascades are activated as a result of meiotic recombination errors in spermatogenesis and oogenesis; 2) to genetically test whether specific pro-apoptotic pathway genes are required for recombination-defective meiocyte cell death and to determine whether the observed sexual dimorphism in cell cycle responses is a consequence of differential use of these genes. ? ? ?
| Cole, Francesca; Baudat, Frédéric; Grey, Corinne et al. (2014) Mouse tetrad analysis provides insights into recombination mechanisms and hotspot evolutionary dynamics. Nat Genet 46:1072-80 |
| Cole, Francesca; Kauppi, Liisa; Lange, Julian et al. (2012) Homeostatic control of recombination is implemented progressively in mouse meiosis. Nat Cell Biol 14:424-30 |
| Shakya, Reena; Reid, Latarsha J; Reczek, Colleen R et al. (2011) BRCA1 tumor suppression depends on BRCT phosphoprotein binding, but not its E3 ligase activity. Science 334:525-8 |
| Cole, Francesca; Jasin, Maria (2011) Isolation of meiotic recombinants from mouse sperm. Methods Mol Biol 745:251-82 |
| Cole, Francesca; Keeney, Scott; Jasin, Maria (2010) Comprehensive, fine-scale dissection of homologous recombination outcomes at a hot spot in mouse meiosis. Mol Cell 39:700-10 |
| Cole, Francesca; Keeney, Scott; Jasin, Maria (2010) Evolutionary conservation of meiotic DSB proteins: more than just Spo11. Genes Dev 24:1201-7 |
