Our address

portrait

CNRS - Centre de Génétique Moléculaire - UPR 3404

Avenue de la Terrasse - Bât. 24

91198 GIF-SUR-YVETTE Cedex

FRANCE

Phone : 33 (0)1 69 82 43 87

The group

Pierre Libeau, Assistant-ingénieur

Kathrin Marheineke, Chargée de Recherche, CNRS

Pierre Priam, étudiant

Ilan Theurillat, étudiant

Raphaelle Trouslard, étudiante

DNA fibers

Research interests

DNA replication is an essential step in cell proliferation. In higher eukaryotes, DNA replication starts at thousands of sites called replication origins.

The spatial and temporal activation of these origins during S phase is only poorly understood but changes during differentiation and development. Cell cycle checkpoints protect the genome stability during S phase when DNA replication is perturbed by DNA dammage or stalled replication forks.

We have shown that the checkpoint kinases ATR/ATM are implicated in the presence and absence of external replication stress in the control of the replication program.

We use the Xenopus ( (Xenopus laevis) in vitro system in order to study the spatio-temporal control of DNA replication in the presence and absence of replication stress. In this system sperm nuclei replicate efficiently in egg extracts. In order to visualize replication origin activation we use a DNA fiber stretching technique called molecular combing of DNA.

The group started in September 2010 at the CGM. We benefit from the fundings of the Association for cancer research (ARC) and the Ligue against Cancer.

A PhD project is available (see ED GGC website).

A motivated candidate for a post-doc project can contact K. Marheineke.

Selected publications

- Despras, E., Daboussi, F., Hyrien, O., Marheineke K., Kannouche, PL. (2010) ATR/Chk1 pathway is essential for resumption of DNA synthesis and cell survival in UV-irradiated XP variant cells. Hum Mol Genet, 19 (9) 1690-701.

- Krude, T., Gardiner, T., Hyrien, O., Marheineke, K. (2009) Non-coding human Y RNAs are required for the establishment, but not the elongation of chromosomal DNA replication forks. J Cell Science, 122 (Pt 16) 2836-45.

- Marheineke, K., Goldar, A., Krude, T., Hyrien, O. (2009) Use of DNA combing to study DNA replication in Xenopus and human cell-free systems. Methods in Molecular Biology, DNA replication: Methods and Protocols, 521, 575-603.

- Labit, H., Perewoska, I, Germe, T., Hyrien O., Marheineke K. (2008) DNA replication timing is deterministic at the level of chromosomal domains but stochastic at the level of replicons in Xenopus egg extracts. Nucleic Acids Res, 36 (17) 5623-34

- Goldar, A., Labi,t H., Marheineke, K., Hyrien, O. (2008) A dynamic stochastic model for DNA replication initiation in early embryos. PLoS ONE, 3 (8).

- Labit H., Goldar, A.,Guilbaud, G., Douarche C., Hyrien O., Marheineke K., (2008) A simple and optimized method of producing silanized surfaces for FISH and replication mapping on combed DNA fibers. BioTechniques, 45, 649-658.

- Teer, JK., Machida, YJ., Labit, H., Novac, O., Hyrien, O., Marheineke K., Zannis-Hadjopopoulos M., Dutta, A. (2006) Low levels of Orc2 in human cells decrease pre-RC formation and result in a G1 cdk activation defect. J Biol Chem, 281, 6253-6260.

- Marheineke, K., Hyrien O., Krude T. (2005) Visualisation of bidirectional initiation of chromosomal DNA replication in a human cell free system. Nucleic Acids Res, 33, 6931-6941.

- Marheineke, K., Hyrien O. (2004) Control of replication origin density and firing time in Xenopus egg extracts : implication of a caffeine-sensitive, ATR dependent checkpoint. J Biol Chem, 279, 28071-28081.

- Hyrien O., Marheineke K. , Goldar A. (2003) Paradoxes of eukaryotic DNA replication: MCM proteins and the random completion problem. Bioessays, 25, 116-125.

- Marheineke, K., Hyrien O. (2001) Aphidicolin triggers a block to replication origin firing in Xenopus egg extracts. J Biol Chem, 276, 17092-17100.