Mammalian Meiosis and an Essential Protein
Mammals produce sperm or egg cells through meiosis, a type of cellular division that generates four genetically unique sex cells. A multistep process, meiosis entails two cellular divisions and involves an organism’s entire genome. Especially critical is the first meiotic division, during which homologous chromosomes of maternal and paternal origin pair up, exchange genetic material, and then split apart again. Errors are possible at every step and are responsible for most prenatal losses and birth defects in humans.
Paula Cohen, Biomedical Sciences, is elucidating the molecular mechanisms that drive and regulate meiosis. Cohen focuses on crossovers, a process that tethers homologous chromosomes and facilitates the trading of genes to ensure variation among an organism’s sex cells. In order for meiosis to proceed, crossovers must progress precisely with regard to their number, timing, and location.
Cohen’s lab has identified two proteins with a critical role in designating where crossovers will occur. With this grant, Cohen’s lab is turning attention to cyclin n-terminal domain-containing-1 (CNTD1), a protein essential for regulating the number of crossovers. Computer analysis suggests that CNTD1 may have two distinct functions at different points in the process. Using mouse models, Cohen is investigating the dual activity of CNTD1 as part of a larger effort to map the molecular interactions that orchestrate crossovers.
This project, which has received continuous funding for 18 years, is explaining in molecular detail the complex and delicate processes that contribute to the frequency of errors that occur during meiosis in humans and other higher mammals.
NIH Award Number: 2R01HD041012-17