Recombination

Recombination is an important and essential mechanism that contributes to genome maintenance as well as horizontal DNA acquisition. While the process has been well-studied biochemically, it is less understood how recombination occurs inside the cell and how it is regulated. 

We developed a system to induce site-specific DNA double-strand breaks in a controlled manner on the chromosome. With this, we leveraged high spatial and temporal resolution imaging tools to track recombination dynamics inside living cells. Characterization of in vivo double-strand break repair revealed that recombination was efficient between distant homologous sequences, even in the absence of DNA replication (PMID 26240183; 28489851).

With this method, we provided a solution to the problem of homology search – how do sister chromatids find each other inside the cell? We discovered an essential role for the Structural Maintenance of Chromosome family protein RecN in driving RecA movement for long-distance homology search (PMID 36346847). More recently, we have combined our imaging approaches with polymer modeling in collaboration with the Goloborodko group at IMBA, Vienna to probe the molecular underpinnings of this mechanism.  

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We are now investigating the organization of recombination proteins on DNA, as well as additional players in the complex. We are also looking at how the recombination machinery interfaces with phages.  ​​