Periodic Reporting for period 2 - EpiRep (Mechanism of nucleosome assembly during DNA replication)
Période du rapport: 2021-06-01 au 2022-11-30
Cell division maintains life for all living organisms. Complex molecular mechanisms are in place to ensure accurate cell division. Deregulation of these mechanisms leads to uncontrolled divisions that may lead to environmental disasters or cause diseases such as cancer. A critical step in cell division occurs when the genome is replicated. This process copies the genetic information that will be inherited by the daughter cells. Here, copying of genome sequence is coupled to copying of its structural organization into chromatin. Here we study how these two processes are coupled at the molecular level.
So far, we have developed new assays to study how chromatin organization is copied during genome replication. We have used recombinant proteins to reconstitute these mechanisms biochemically, which allow us to carefully quantify and understand their molecular underpinnings. We have developed new methods to study chromatin assembly coupled to DNA synthesis. We have also established new cell lines to modulate these processes in cells and investigate their cellular consequences. We have applied these tools to elucidate the molecular mechanism that drive genome and chromatin replication, using protein mutants. So far, we find differential crosstalk between the genome and chromatin machineries on the two replicated DNA strands.
Our contributions go beyond the state of the art. First, we have developed methods that enable quantitative measurements on a vital process in biology. Second, we identify direct crosstalk between the genome and chromatin machineries that explain the molecular links between these processes. Finally, we are elucidating cellular responses to errors in these events with unprecedented temporal control. We envision that applying these new tools and knowledge will bring important discoveries in the second part of the project.