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Jean  Gautier
Jean Gautier
Associate Professor, Genetics & Development


Address: 1130 St. Nicholas Avenue ICRC Room 602 New York NY 10032
Phone: 212-851-4564
Fax: 212-851-5284
E-mail:

jg130@columbia.edu

Education and Training:
Ph.D. 1983, Toulouse University
Dr. Sc. 1988, Toulouse University
Postdoctoral Fellowship 1988-89, University of Colorado
Postdoctoral Fellowship 1989-92, UC San Francisco
Affiliations:
bullet  Department of Genetics and Development
bullet  Graduate Program in Biomedical Sciences
bullet  Insitute for Cancer Genetics
Training Activities:
bullet  Integrated Program in Cellular, Molecular and Biophysical Studies
Research Summary:
(800 words, max)
Maintenance of genome stability: DNA replication and response to DNA damage

Current Research:
Much of our work focuses on the mechanisms that control the proper order, timing and accuracy of cell cycle phases. These mechanisms are essential to maintain the integrity of the genome and the fidelity of transmission of the genetic material throughout cell generations. We use the eggs and embryos of the frog Xenopus laevis and cell-free extracts derived from these as a simple model system to gain important molecular and biochemical insights on cell cycle and checkpoints regulation. In addition, we use mammalian cells in culture as well as mouse models to study some of the biological responses to DNA damage.

Using these model systems we are addressing the following questions:

A) How is the ordered progression of the cell cycle phases maintained, how is DNA replication restricted to once per cell cycle? We are conducting biochemical studies to understand how the proteins at the origins of replication (pre-replicative complex or pre-RC) are assembled and how they function in a cell cycle regulated manner.

B) How is the cell cycle regulated following DNA damage? We are studying the function of the ATM (Ataxia Telangiectasia Mutated) protein. In particular, we have established a novel cell-free system that allows us to study the biochemical role of ATM in vitro.

C) What are the mechanisms that regulate exit from mitosis and chromosomes segregation? We are investigating the molecular nature of the checkpoints that prevent inappropriate chromosome segregation. We are also investigating the cross talk between protein kinase A (PKA) and the cyclin-dependent kinases that regulate mitosis.

D) We are studying the biochemical reactions involved in the repair of several types of DNA damage using Xenopus cell-free extracts.
Publications:
(6 max)
1. Dupre A, Boyer-Chatenet L, Gautier J.: (2006) Two-step activation of ATM by DNA and the Mre11-Rad50-Nbs1 complex.   Nat. Struct. Mol. Biol  13(5): 451-457

2. Shechter D, Gautier J.: (2005) ATM and ATR checks in on origins: a dynamic model for origin selection and activation.  Cell Cycle  4(2): 235-238

3. Ying CY, Gautier J. : (2005) The ATPase activity of MCM2-7 is dispensable for pre-RC assembly but is required for DNA unwinding.  Embo Journal  24(24): 4334-4344

4. DiVirgilio M, Gautier J.: (2005) Repair of double-strand breaks by nonhomologous end joining in the absence of Mre11.  J. Cell Biology  171(5): 765-771

5. Costanzo V., Paull T., Gottesman M. and Gautier J.: (2004) Mre11 assembles linear DNA fragments into DNA damage signaling complexes. PLoS Biology.  PLoS Biology  2: 600-609

6. Shechter D. Costanzo V. and Gautier J.: (2004) Regulation of DNA replication by ATR: signaling in response to DNA intermediates.   DNA Repair   3(8-9): 901-908

URL for lab page:
 http://gautier.openwetware.org/

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