Michelle Debatisse (Institut Curie)

Mechanism of Common Fragile Site instability: Crosstalk between replication and transcription programs
Nov 23, 2015, 12:00 pm12:00 pm
Thomas Laboratory, 003
Free and open to the university community and the public


Michelle Debatisse
Unit Director, Dynamics of Genetic Information
Institut Curie


Event Description

Common fragile sites (CFSs) are loci that recurrently display chromosome breaks upon replication stress, and are now correlated with genomic rearrangements formed in tumors. Presently, there is a large consensus to consider that breaks occur at CFSs when cells enter mitosis with incompletely replicated sites. However, the rationale for this delayed replication completion is still debated. We have recently shown that CFSs are epigenetically defined and that fragility is associated with tissue-specific replication patterns. In addition, our extensive profiling of CFSs in cells of various tissues has confirmed and expanded previous observation that most CFSs host very long genes, raising the question of whether transcription impacts the replication program and CFS instability. To address this question, we have inhibited or stimulated large gene expression in human fibroblasts and DT40 chicken cells using TALEs or genome editing. We have shown that transcription of large genes impacts the stability of cognate CFS and identified modulation of replication timing as one major mechanism by which transcription regulates CFS instability. 

Virginia Zakian, Department of Molecular Biology
Event Category
Butler Seminar Series