Institut Jacques Monod

Abstract
he information contained in DNA is continuously subjected to degradation, for instance by processes which lead to direct chemical damage of DNA or incorporation of errors during genome replication.  To compensate these processes, DNA is continuously being repaired.  DNA repair is often a complex process, typically requiring numerous proteins which in succession must reliably and robustly identify DNA damage, remove DNA damage, and ultimately  replace damaged DNA with new, intact DNA.  Thus DNA repair is also often a multi-step process, making detailed kinetic analysis and identification of rate-limiting features particularly challenging.  Single-molecule approaches can be particularly helpful for studying multi-step reactions in real-time, allowing one to circumvent molecular desynchronization and population averaging inherent to an ensemble, macroscopic sample.  In this talk we will discuss the use of single-molecule experimentation to study DNA repair in real-time.  We will describe the use of nanomanipulation methods to monitor in real-time the DNA deformations resulting from defined states of a protein-DNA complex, and fluorescence methods to simultaneusly monitor in real-time the compositional state of the protein-DNA complex.  We will illustrate these methods by focusing on “bottom-up” reconstruction at single-molecule resolution of complex nucleotide-excision repair pathways such as post-replicative mismatch repair and transcription-coupled DNA repair. 

Terence Strick obtained a Bachelor's degree in Physics at Princeton University and a PhD in Molecular and Cellular Biology at the Ecole Normale Superieure in Paris where he developped the magnetic trapping approach to single-molecule experimentation [1,2].  He then worked as a Fellow at Cold Spring Harbor Laboratory, after which he obtained a reserach position at the Centre National de la Recherche Scientifique in France.  He has been Principle Investigator of the Biomolecular Nanomanipulation Group at the Institut Jacques Monod in Paris since 2004.  Research in the group has focused on developping real-time, single-molecule approaches for detecing protein-DNA interactions in real-time, with a particular interest in DNA transcription [3], replication [4] and repair [5].
 
[1] Strick et al., (1996) Science 271: 1835—1837
[2] Strick et al., (2000) Nature 404: 901—904
[3] Revyakin et al., (2006) Science 314 : 1139—1143
[4] Zorman et al., (2012) Nucleic Acids Res., 40 : 7375—7383
[4] Ho Wan et al., (2012) Nature 490 : 431—434
 
Lab website
http://www.ijm.fr/en/research/research-groups/biomolecular-nanomanipulation/

联系人：联系人：李明 研究员（010-82649058）