Meiotic DNA repair and Genome Stability

Research team members

Nicola Silva, PhD.

Group leader

phone: +420 549 49 8033
e‑mail:

Genotoxic insults can arise from both environmental and cell metabolism-associated processes, which left unresolved can lead to cell death, cancer and sterility.

Importantly, during gametogenesis programmed induction of DNA double strand breaks (DSBs) is elicited in order to promote homologous recombination-mediated repair and formation of physical attachments between the parental chromosomes (homologs) arising from crossover (CO) events. COs promote genetic variability but most importantly they allow faithful chromosome segregation, hence are crucial to generate functional gametes.

In most species, the amount of DSBs largely exceeds the final number of COs, suggesting that many breaks are repaired through CO-independent pathways.

Several proteins are involved at different steps to achieve faithful DNA repair during gametogenesis and most of them are conserved throughout evolution, allowing the study of their conserved function in simple model organisms.

In the lab we employ Caenorhabditis elegans, a non-parasitic nematode, as a model system to study meiotic DNA repair. C. elegans bears several features which make it one of the most powerful systems to study chromosome metabolism in the germline, including easy handling, a transparent body and spatio-temporal synchronization of meiocites in all stages of meiotic prophase I in the gonad.

We combine genetic, biochemistry and high-resolution cytology tools to characterize different factors involved in DSB repair, as well as identify new ones mostly through a biochemical approach. We are particularly interested in unravelling the roles of ubiquitination and ADP-ribosylation in promoting genome stability in developing gametes.

 

Two PhD positions are available for the following topic:

Identification and characterization of factors involved in meiotic DNA double strand breaks repair

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