Replication and Genome Dynamics

 Marcel MECHALI

 IGH - UMR 9004

 141, rue de la Cardonille, 34396 Montpellier

Phone: +33 4 34 35 99 17

Email: marcel.mechali@igh.cnrs.fr

Website

We wish to decipher the genetic and epigenetic elements that define the DNA replication origins in metazoans. A main goal is to question the involvement of the origin's code in cell identity and development. We also aim to dissect the molecular mechanisms used to build a chromosomal DNA replication origin and unravel epigenetic mechanisms that control the organization of chromatin domains for replication. Both mouse and Drosophila systems are used for this purpose. A second main axis is to identify and characterize new proteins involved in the control of DNA replication. We exploit in-vitro systems derived from Xenopus eggs, and mouse cell systems for this characterization and functional assays.

Keywords: DNA replication/Chromatin/Xenopus/Mouse/Development

Main publications

• Ganier, O., Bocquet, S., Peiffer, I., Brochard, V., Arnaud, P., Puy, A., Jouneau, A., Feil, R., Renard, J.P., and Méchali M. (2011) Synergic reprogramming of mammalian cells by combined exposure to mitotic Xenopus egg extracts and transcription factors. Proc Natl Acad Sci U S A., 108, 17331-17336.
• Cayrou C., Coulombe P, Vigneron A., Stanojcic S., Ganier O., Peiffer I., Rivals E., Puy A., Laurent-Chabalier S., Desprat R., and Méchali M. (2011) Genome-scale analysis of metazoan replication origins reveals their organization in specific but flexible sites defined by conserved features. Genome Res., 9, 1438-1449.
• Nishiyama A, Frappier L, Méchali M. (2010) MCM-BP regulates unloading of the MCM2-7 helicase in late S phase. Genes and Dev, 25, 165-175. Article recommended as Must Read by The Faculty of 1000.
• Méchali, M, (2010), DNA replication origins: many choices for appropriate answers. Nature Rev Mol Cell Biol, 11, 728-738.
• Lutzmann M, and Mechali M. (2008) MCM9 binds Cdt1 and is required for the assembly of prereplication complexes. Mol Cell, 31, 190-200. This article has been recommended as Must Read by The Faculty of 1000.
• Lemaitre, JM., Danis, E., Y Vassetzky, Y., Pasero. P., and Méchali., M. (2005) Mitotic remodeling of the replicon and chromatin structure, Cell, 123, 787-801. This article has been the subject of 6 "Research Highlights" in Cell, Nature, Nature Cell Biology, Nature Rev. Mol. Cell Biol., Nature Methods, J. Cell Biol. It has been recommanded as Outstanding by The Academy of 1000.
• Maiorano, D, Cuvier, O., Danis, E., and Méchali, M. (2005) MCM8 is an MCM2-7 related protein that functions as a DNA helicase during replication elongation and not initiation. Cell, 120, 315-28. This article has been recommended as Exceptional by the Faculty of 1000.
• Danis, E., Brodolin, K., Menut, S., Maiorano, D., Girard-Reydet, C. and Méchali , M. (2004). Specification of a DNA replication origin by a transcription complex. Nature Cell Biol., 6, 721-730. This article has been the subject of an Editors' Choice in Science.
• Lemaître, J.M., Bocquet, S., and Méchali, M. (2002) Competence to replicate in the unfertilized egg is conferred by Cdc6 during meiotic maturation. Nature, 419, 718-722. This article received two commentaries in Bio Essays (2003), 25, 313-316 , and Trends in Cell Biology (2003), 302, 728-734). It has been recommended as Exceptional by the Faculty of 1000.
• Maiorano, D., Moreau, J., and Méchali, M. (2000) XCDT1 is required for the assembly of pre-replicative complexes in Xenopus laevis. Nature, 404, 622-625. This article had a News and Views in Nature 404, 560-561.