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Mechanism of repetitive sequence instability

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Date : 28/05/2010

Internship proposal for : Master 1 or Master 2

Laboratory

DNA synthesis associated pathologies
UMR 7592 Institut Jacques Monod CNRS, INSERM, Paris Diderot
15 rue Hélène Brion
75205 Paris cedex 13
Director : Giuseppe Baldacci
Website : http://www.ijm.fr/fr/ijm/recherche/equipes/pathologies-replication/
Main discipline : Molecular biologyBiochemistry

Supervisor

Emmanuelle Delagoutte
email : Cet e-mail est protégé contre les robots collecteurs de mails, votre navigateur doit accepter le Javascript pour le voir
phone : +33 157278073

  Subjects / Tools-Methodologies

1 : genome instability/biochemistry - protein purification
2 : DNA replication and repair/molecular biology
3 : DNA structure/biophysics

Summary of lab's interests

A variety of genetic diseases such as cancers or neurological disorders are due to mutations in repetitive sequences. Our research aims at elucidating the mechanisms of repetitive sequence instability. Recent studies have implicated the DNA polymerase as a major actor in repetitive sequence instability. In the cell, DNA polymerases play an essentiel role not only in DNA replication but also in DNA repair. Our goal is therefore to understand how repair and replicative DNA polymerase cope with repetitive sequences.

Summary of project

In the laboratory we perform DNA synthesis assays with replicative or repair DNA polymerases and characterize the DNA polymerase activity (rate, fidelity, etc) across various repetitive DNA sequences. Furthermore, considering that a DNA polymerase never acts on its own but is assisted by other cellular proteins (single stranded DNA binding (SSB) proteins, processivity factor, etc), we characterize the effect of such auxiliary proteins on the DNA polymerase activity. The project of the student who will join our laboratory will consist of characterizing the behavior of a variety of DNA polymerases (including T4 DNA polymerase, yeast DNA polymerase delta and epsilon) across structure forming and non structure forming repetitive sequences in the presence of auxiliary proteins (helicase, processivity factor and SSB proteins) or not.