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HOTMEIOSIS Report Summary

Project ID: 322788
Funded under: FP7-IDEAS-ERC
Country: France

Mid-Term Report Summary - HOTMEIOSIS (Meiotic recombination: How, where and why? Mechanisms and Implications)

Our aim is to understand some important properties of the transmission of the genetic information through generations. The two remarkable properties of the genome that is transmitted through gametes are on one hand its stability, a prerequisite for a healthy progeny, and on the other hand its variation due to the new combinations of paternal and maternal chromosomes that are created during the process called meiosis.
We aim to understand the molecular control of the events involved in these processes.
We have identified in 2010 a component from a molecular machinery that plays a key role in the control of the genetic diversity that is generated during meiosis and that impact on the association between genes along chromosomes. This component is the PRDM9 protein and we have now demonstrated one of its activity which is to modify histones. We have explored the genetic diversity of PRDM9 in wild mice which turns out to be exceptionally high and which suggests that the gene coding for this protein is rapidly evolving and under positive selection.
In parallel, we aim to understand the control of the stability of the genome as it is transmitted in gametes. This question is stimulated by the fact that paradoxically, a large number of breaks are induced in the DNA of spermatocytes and oocytes. A molecular machinery is somehow specifically activated in these cells and this activity must be highly regulated in order to make sure that all these breaks are properly repaired such as to avoid alterations in the genome. In our effort to characterize this molecular machinery we have very recently identified an essential novel component, TopoVIB-like, which was searched for many years, and that illuminates how breaks in the DNA are generated during meiosis.

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