Turner lab Sex Chromosome Biology Laboratory
: Germ cell surveillance
Identifying surveillance mechanisms that eliminate defective germ cells
Our early work discovered that during meiosis, asynapsed chromosomes are transcriptionally inactivated, in a process called meiotic silencing. Work in our lab provided the first evidence that meiotic silencing can be pathogenic in human fertility.
In order to investigate the mechanisms of meiotic silencing in greater depth, we utilised an endogenous process called meiotic sex chromosome inactivation. In this process, the male X and Y chromosomes are routinely transcriptionally silenced during meiosis, due to the limited sequence homology contained between the two sex chromosomes. We discovered epigenetic mechanisms regulating the silencing process. We found that DNA-damage proteins ATR and TOPBP1 recruit TRIM28 and methyltransferase SETDB1, which deposits the repressive H3K9me3 mark on the sex chromosomes. We also discovered that ATR, with the help of ATM, regulates meiotic synapsis and recombination. The process of meiotic recombination is essential because defects cause mutations and aneuploidies in the next generation of offspring. We discovered that BCL-2 family members PUMA, NOXA and BAX are critical in the recombination checkpoint in oocytes.
