Meiosis & Genome Stability Lab

Research Interests

During gametogenesis cells enter a developmental program known as meiosis in order to produce haploid gametes. Meiotic cells halve their chromosome number in a process requiring homologous recombination. Meiotic recombination is initiated through the programmed introduction of hundreds of Double Strand Breaks (DSBs) in the DNA catalysed by the Spo11 complex. Spo11 is a Topoisomerase II-type endonuclease which catalyses DSBs within discrete regions in the genome known as hotspots. Presence of DSBs at these hotspots triggers the activation of a family of conserved kinases, ATM/ATR, required for maintaining genome integrity. These kinases phosphorylate multiple substrates, including components of the Spo11 complex, like Rec114. Phospho-Rec114 downregulates Spo11 activity at most hotspots, likely precluding new DSBs to be catalysed nearby. ATM/ATR also phosphorylate Hop1, a structural component of the Synaptonemal Complex (SC). Phosphorylation of Hop1 at multiple S/T[Q] sites is required to ensure Inter-homolog recombination and checkpoint activity, crucial processes for accurate DSB repair in meiosis. Irrespective of these recent advances, there are still many unknown functions and targets of ATM/ATR during meiosis. It will be vital to identify most of those roles in order to understand defects that elicit aneuploidies or mutations in the gametes, a source of many congenital disorders, infertility and cancer.