DNA replication, DNA repair and the DNA damage response in the maintenance of genomic integrity
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.
Specifically, we are studying:
- The mechanism of DNA double-strand break (DSB) repair, in particular the early processing events that are critical to determine repair pathway choice. We utilize biochemical approaches in cell-free extracts derived from the eggs of the vertebrate, Xenopus laevis, proteomics analysis as well as small molecules that regulate the response to DSBs.
- The mechanism(s) of DNA Inter-strand Crosslink (ICL) repair. These lesions are generated by several classes of successful chemotherapeutic drugs. Understanding signaling from these lesions and their modes of repair is critical to develop more effective compounds and to circumvent resistance.
- DNA replication stress and DNA damage resulting from oncogene activation. We are focusing on the case of c-Myc
- 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: 657-667
- *Dupre A., *Boyer-Chatenet L., Sattler RM., Modi A., Lee JH., Nicolette M., Kopelovich L., Jasin M., Baer R., Paull T. and Gautier J: (2008) A forward chemical genetic screen reveals an inhibitor of the Mre11-RAD50-Nbs1 complex. Nature Chem. Biol 4: 119-125
- Williams H., Gottesman M. and Gautier J. : (2012) Replication-independent repair of interstrand crosslinks.. Molecular Cell 47: 140-147
- 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: 1629-1639
- c. Rozier, L., Guo, Y., Peterson. S., Sato, M., Baer, R. Gautier, J*. and Y. Mao*: (2013) The MRN-CtIP pathway is required for metaphase chromosome alignment. Molecular Cell 49: 1097-1107
- Link to complete list of publications:: https://scholar.google.com/citations?user=OGR--C0AAAAJ&hl=en.