Eugene Gladyshev: Towards the general mechanism of recombination-independent recognition of DNA homology
May 18, 2018
09:00 - 10:00
Eugene Gladyshev from the Pasteur Institute in Paris, France
Here, you will find further information on the speaker: https://research.pasteur.fr/en/team/fungal-epigenomics/
The ability of apparently intact homologous DNA duplexes to specifically associate with one another in vivo and in vitro has been implicated in recombination-independent pairing of homologous chromosomes (or selected chromosomal regions) in meiosis and in somatic cells. The general mechanism(s) by which DNA sequence homology can be searched and recognized in such situations, i.e., in the absence of DNA breakage and recombination, represent(s) one of the most fundamental unanswered questions in molecular biology. Using the process of Repeat-Induced Point mutation (RIP) in the fungus Neurospora crassa as a model system, we previously showed that DNA homology can be recognized in the cell by a molecular approach that is cardinally different from the known recombination-mediated pathway, and which likely involves direct pairing of homologous double-stranded DNA molecules. We also showed that RIP can be carried out by a conserved epigenetic pathway that mediates heterochromatic silencing of repetitive DNA across the entire eukaryotic domain, raising a possibility that the newly uncovered mode of homologous dsDNA-dsDNA pairing can provide a general signal for heterochromatin assembly on repetitive DNA. In our ongoing work, we now find that RIP shares all its homology-recognition principles with Meiotic Silencing by Unpaired DNA (MSUD), which routinely detects gene-sized DNA fragments present on only one of the two homologs. These findings hint at an intriguing possibility that the proposed recombination-independent dsDNA-dsDNA interactions may also be involved in promoting homologous chromosome pairing in meiosis, thus emerging as a general, perhaps fundamental, mode of DNA homology search and recognition.