Jean Gautier, PhD
Dr. Jean Gautier is a recognized leader in the field of genome stability. His long-term research goal is to understand the mechanisms driving genomic instability leading to oncogenesis. His labâ€™s work involves DNA repair, DNA replication and oncogene-driven genomic stress.
Dr. Gautierâ€™s research has been continuously funded by federal grants throughout his 20+ years at Columbia University. Currently, funding for his laboratory comes exclusively from the National Cancer Institute, including a Program Project (P01) for which he is the principal investigator and an Outstanding Investigator Award (R35).
His laboratory was the first to demonstrate the intrinsic DNA helicase activity of the MCM proteins. His laboratory characterized the molecular mechanisms of ATM and ATR activation, describing the role of the Mre11 nuclease for which his laboratory isolated the first small molecule inhibitor. More recently, his lab established that nuclear actin-based mobility shapes the spatial organization of the nucleus by generating repair domains essential for homologous recombination.
In 2015, Dr. Gautier was received an Outstanding Investigator Award from the National Cancer Institute and was named a Rothschild Fellow from the Curie Institute.
The main objective of our research is to better understand the molecular mechanisms responsible for the maintenance of genome stability. These controls are lost in cancer, which is characterized by genomic instability.
The laboratory employs diverse experimental approaches to elucidate the role of genome instability in cancer. Cell-free extracts derived from the egg of the frog Xenopus laevis are used as a simple model system to study processes that govern genome stability, including DNA replication control, DNA repair, and the cellular response to DNA damage. In addition, cultured mammalian cells and mouse models are exploited to analyze biological responses to DNA damage. Several specific questions are currently being addressed in his lab. First, what repair pathways are involved in processing DNA lesions induced by cancer chemotherapeutic drugs? Specifically, Dr. Gautier’s lab examines double-strand break repair and DNA inter-strand crosslink repair. The second is, what conditions favor mis-repair of DNA and lead to chromosome rearrangements? The third is, what are the molecular origins of oncogene-induced genomic stress?
Williams H., Gottesman M. and Gautier J. (2012). Replication-independent repair of interstrand crosslinks. Molecular Cell, 47: 140-7.
Peterson, S., Li, Y., Wu-Baer, F., Chait, B., Baer, R., Yan, H., Gottesman, M. and Gautier J. (2013). Activation of DSB processing requires phosphorylation of CtIP by ATR. Molecular Cell, 49: 657-67.
Srinivasan, S., Dominguez-Sola, D., Wang, L.C., Hyrien, O. and Gautier, J. (2013) “Cdc45 is a critical effector of Myc-dependent DNA replication stress”. Cell Reports, 3:1629-39.
Sato, M., Rodriguez-Barrueco R., Yu J., Do C., Silva JM and Gautier J. (2015) “MYC is a critical target of FBXW7. Oncotarget 6: 3292-305.
Aparicio, T., Baer, R., Gottesman, M. and Gautier, J. (2016) “MRN, CtIP, and BRCA1 mediate repair of topoisomerase II–DNA adducts”. The Journal of Cell Biology. 212: 399-408.
Kato N., Kawasoe Y., Williams H., Coates E., Roy U., Shi Y., Beese L., Scharer O., Yan H., Gottesman M., Takahashi T. and Gautier J. (2017) Sensing and processing of DNA interstrand crosslinks by the mismatch repair pathway. Cell Reports. 21: 1375-1385.
Link to complete list of publications:: https://scholar.google.com/citations?user=OGR--C0AAAAJ&hl=en&oi=ao