Research
Our main objective is to understand the relationships between gene transcription and genome stability. In particular, we seek to understand how two major transcription by-products, transcription-associated topological stress and the formation of stable DNA:RNA hybrids, can impact genome stability in mitosis.
Our current project is funded by a “Chaire d’Excellence“ from the ANR. Its main objective is to describe how the formation of stable DNA:RNA hybrids impacts genome stability through cell division. Transcription is classically thought as producing an RNA transcript that immediately leaves the DNA template as the transcription machinery moves along. On occasion, the transcribed RNA can remain hybridized to the template DNA strand, forming a stable DNA:RNA hybrid. The formation of such stable DNA:RNA hybrids in Eukaryotic genomes was thought until recently to be a rare event associated mostly with detrimental consequences. DNA:RNA hybrid formation can stall transcription and interfere with DNA replication, leading to DNA breaks and genome instability. In humans, transcription-induced rearrangements have been linked to numerous cancers.
Our current project is funded by a “Chaire d’Excellence“ from the ANR. Its main objective is to describe how the formation of stable DNA:RNA hybrids impacts genome stability through cell division. Transcription is classically thought as producing an RNA transcript that immediately leaves the DNA template as the transcription machinery moves along. On occasion, the transcribed RNA can remain hybridized to the template DNA strand, forming a stable DNA:RNA hybrid. The formation of such stable DNA:RNA hybrids in Eukaryotic genomes was thought until recently to be a rare event associated mostly with detrimental consequences. DNA:RNA hybrid formation can stall transcription and interfere with DNA replication, leading to DNA breaks and genome instability. In humans, transcription-induced rearrangements have been linked to numerous cancers.
Recent evidence now suggests that DNA:RNA hybrids actually form at
thousands of loci in human cells during an unperturbed cell-cycle. These
hybrids have been implicated in a wide range of processes such as the
establishment of chromatin modification patterns, the regulation of gene
expression, transcription termination, and the local regulation of chromatin
compaction. These new observations dramatically alter current ideas about the
role of DNA:RNA hybrids in Eukaryotic biology and demonstrate that they are not
solely a toxic transcriptional by-product but also represent an essential
signalling platform for various essential processes. What distinguishes DNA:RNA
hybrids representing a threat for DNA replication and genome stability from
DNA:RNA hybrids playing a regulatory role is still unknown.
In the lab, we are using the fission yeast Schizosaccharomyces pombe to unravel the different functions of
DNA:RNA hybrids. In particular, we seek to:
1. Develop techniques that can reliably map DNA:RNA hybrids genome-wide.
2. Use yeast genetics to identify factors that regulate the formation and the function of DNA:RNA hybrids.
3. Characterize the impact that DNA:RNA hybrids have on chromosome organization and chromosome transmission in mitosis.
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| fission yeast cells |
1. Develop techniques that can reliably map DNA:RNA hybrids genome-wide.
2. Use yeast genetics to identify factors that regulate the formation and the function of DNA:RNA hybrids.
3. Characterize the impact that DNA:RNA hybrids have on chromosome organization and chromosome transmission in mitosis.
