Meiosis and recombination

Genome dynamics

In sexually reproducing species, meiosis allows the formation of haploid gametes from diploid cells. The halving of the DNA content results from a specialized cell cycle, where a single phase of DNA replication is followed by two divisions. The reductional segregation of homologous chromosomes (homologues) at the first meiotic division requires the establishment of connections between homologues. In most species, these connections are established during a long and specialized prophase by reciprocal exchanges between homologues. These exchanges, also called crossing over, result from a highly regulated homologous recombination pathway that drives the recognition and interaction between homologues and the formation of at least one crossing over per homologue pair. Crossovers also generate new allele combinations and thus increase genetic diversity and contributes to genome evolution. The absence of crossover leads to chromosome segregation defects and sterility, and alteration of the meiotic recombination pathway can lead to genome rearrangements and aneuploidy.

Our team is investigating several aspects of the mechanism and regulation of meiotic recombination and its evolutionary implication using the mouse as a model system. Meiotic recombination events are initiated by the formation of DNA double-strand breaks (DSBs, several hundred per nucleus in mice), the repair of which leads to both crossovers and non-crossovers (gene conversion without crossover). The main steps and factors involved in this pathway are evolutionary conserved.

Figure 1



PRDM9 activity depends on HELLS and promotes local 5-hydroxymethylcytosine enrichment.

Imai Y, Biot M, Clément J, Teragaki M, Urbach S, Robert T, Baudat F, Grey C, de Massy B

Reading the epigenetic code for exchanging DNA.

Biot M, de Massy B

Mouse ANKRD31 Regulates Spatiotemporal Patterning of Meiotic Recombination Initiation and Ensures Recombination between X and Y Sex Chromosomes.

Papanikos F, Clément JAJ, Testa E, Ravindranathan R, Grey C, Dereli I, Bondarieva A, Valerio-Cabrera S, Stanzione M, Schleiffer A, Jansa P, Lustyk D, Fei JF, Adams IR, Forejt J, Barchi M, de Massy B, Toth A

Sex chromosome quadrivalents in oocytes of the African pygmy mouse Mus minutoides that harbors non-conventional sex chromosomes.

Baudat F, de Massy B, Veyrunes F

Mouse REC114 is essential for meiotic DNA double-strand break formation and forms a complex with MEI4.

Kumar R, Oliver C, Brun C, Juarez-Martinez AB, Tarabay Y, Kadlec J, de Massy B

PRDM9, a driver of the genetic map.

Grey C, Baudat F, de Massy B

PRDM9 Methyltransferase Activity Is Essential for Meiotic DNA Double-Strand Break Formation at Its Binding Sites.

Diagouraga B, Clément JAJ, Duret L, Kadlec J, de Massy B, Baudat F

In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites

Grey C, Clément JA, Buard J, Leblanc B, Gut I, Gut M, Duret L, de Massy B.

The PRDM9 KRAB domain is required for meiosis and involved in protein interactions

Imai Y, Baudat F, Taillepierre M, Stanzione M, Toth A, de Massy B.

TopoVIL : a molecular scissor essential for reproduction

Robert, T, De Massy, B, Grelon, M.

Birth and death of a protein

Clément J, de Massy B

SKAP, an outer kinetochore protein, is required for mouse germ cell development

Grey C, Espeut J, Ametsitsi R, Kumar R, Luksza M, Brun C, Verlhac MH, Suja JÁ, de Massy B

The TopoVIB-Like protein family is required for meiotic DNA double-strand break formation

Robert T, Nore A, Brun C, Maffre C, Crimi B, Bourbon HM, de Massy B

A new light on the meiotic DSB catalytic complex

Robert T, Vrielynck N, Mézard C, de Massy B, Grelon M

Meiotic DNA break formation requires the unsynapsed chromosome axis-binding protein IHO1 (CCDC36) in mice

Stanzione M, Baumann M, Papanikos F, Dereli I, Lange J, Ramlal A, Tränkner D, Shibuya H, de Massy B, Watanabe Y, Jasin M, Keeney S, Tóth A

MEI4: a central player in the regulation of meiotic DNA double strand break formation in the mouse

Kumar R, Ghyselinck N, Ishiguro KI, Watanabe Y, Kouznetsova A, Höög C, Strong E, Schimenti J, Daniel K, Toth A, de Massy B.

Meiosis: early DNA double-strand breaks pave the way for inter-homolog repair

Borde V, de Massy B

Diversity of Prdm9 Zinc Finger Array in Wild Mice Unravels New Facets of the Evolutionary Turnover of this Coding Minisatellite

Buard J, Rivals E, Dunoyer de Segonzac D, Garres C, Caminade P, de Massy B, Boursot P.

Mouse tetrad analysis provides insights into recombination mechanisms and hotspot evolutionary dynamics

Cole F, Baudat F, Grey C, Keeney S, de Massy B, Jasin M.

Human genetics. Hidden features of human hotspots

de Massy B.

Spp1 links sites of meiotic DNA double-strand breaks to chromosome axes

De Massy, B.

Programmed induction of DNA double strand breaks during meiosis: setting up communication between DNA and the chromosome structure.

Borde V, de Massy B.

RNF212 is a dosage-sensitive regulator of crossing-over during mammalian meiosis

Reynolds A, Qiao H, Yang Y, Chen JK, Jackson N, Biswas K, Holloway JK, Baudat F, de Massy B, Wang J, Höög C, Cohen PE, Hunter N.

Drosophila Yemanuclein and HIRA Cooperate for De Novo Assembly of H3.3-Containing Nucleosomes in the Male Pronucleus

Orsi GA, Algazeery A, Meyer RE, Capri M, Sapey-Triomphe LM, Horard B, Gruffat H, Couble P, Aït-Ahmed O, Loppin B.

Dissecting the Structure and Mechanism of a Complex Duplication-Triplication Rearrangement in the DMD Gene

Ishmukhametova A, Chen JM, Bernard R, de Massy B, Baudat F, Boyer A, Méchin D, Thorel D, Chabrol B, Vincent MC, Van Kien PK, Claustres M, Tuffery-Giraud S.

SPO11-Independent DNA Repair Foci and Their Role in Meiotic Silencing

Carofiglio F, Inagaki A, de Vries S, Wassenaar E, Schoenmakers S, Vermeulen C, van Cappellen WA, Sleddens-Linkels E, Grootegoed JA, Te Riele HP, de Massy B, Baarends WM.

Cellular Source and Mechanisms of High Transcriptome Complexity in the Mammalian Testis

Soumillon M, Necsulea A, Weier M, Brawand D, Zhang X, Gu H, Barthès P, Kokkinaki M, Nef S, Gnirke A, Dym M, de Massy B, Mikkelsen TS, Kaessmann H.

Initation of Meiotic Recombination: How and Where? Conversation and Specificities Among Eukaryotes.

De massy, B.

Molecular Basis for the Regulation of the H3K4 Methyltransferase Activity of PRDM9.

Wu H, Mathioudakis N, Diagouraga B, Dong A, Dombrovski L, Baudat F, Cusack S, de Massy B, Kadlec J.

Meiotic recombination in mammals: localization and regulation

Baudat F, Imai Y, de Massy B.

Interallelic and intergenic incompatibilities of the prdm9 (hst1) gene in mouse hybrid sterility

Flachs P, Mihola O, Simeček P, Gregorová S, Schimenti JC, Matsui Y, Baudat F, de Massy B, Piálek J, Forejt J, Trachtulec Z.

The Glucocorticoid-Induced Leucine Zipper (GILZ) Is Essential for Spermatogonial Survival and Spermatogenesis

Romero Y, Vuandaba M, Suarez P, Grey C, Calvel P, Conne B, Pearce D, de Massy B, Hummler E, Nef S.

The Molecular Chaperone Hsp90α Is Required for Meiotic Progression of Spermatocytes beyond Pachytene in the Mouse

Grad I, Cederroth CR, Walicki J, Grey C, Barluenga S, Winssinger N, De Massy B, Nef S, Picard D

What defines the genetic map? The specification of meiotic recombination sites.

Grey C, Sommermeyer V, Borde V, de Massy B

The Impressionistic Landscape of Meiotic Recombination

Lichten, M., de Massy, B.

Dicer1 depletion in male germ cells leads to infertility due to cumulative meiotic and spermiogenic defects.

Romero Y, Meikar O, Papaioannou MD, Conne B, Grey C, Weier M, Pralong F, De Massy B, Kaessmann H, Vassalli JD, Kotaja N, Nef S.

Mouse PRDM9 DNA-Binding Specificity Determines Sites of Histone H3 Lysine 4 Trimethylation for Initiation of Meiotic Recombination.

Grey C, Barthès P, Chauveau-Le Friec G, Langa F, Baudat F, de Massy B.

What determines the localisation of spots of meiotic recombination?

Baudat F, Buard J, Grey C, de Massy B.

PRDM9 Is a Major Determinant of Meiotic Recombination Hotspots in Humans and Mice

Baudat, F., Buard, J., Grey, C., Fledel-Alon, A., Ober, C., Przeworski, M., Coop, G., de Massy, B.

Functional conservation of Mei4 for meiotic DNA double-strand break formation from yeasts to mice

Kumar, R., Bourbon, H.M., De Massy, B.

Prdm9, a key control of mammalian recombination hotspots

Baudat F, Buard J, Grey C, de Massy B.

A single mutation results in diploid gamete formation and parthenogenesis in a Drosophila yemanuclein-alpha meiosis I defective mutant

Meyer, RE., Delaage, M., Rosset, R., Capri, M., Ait-Ahmed, O.

Parallel detection of crossovers and non-crossovers in mouse germ cells.

Baudat, F. and de Massy, B.

Genome-Wide Control of the Distribution of Meiotic Recombination.

Grey C, Baudat F, de Massy B.

Mutation of the mouse Syce1 gene disrupts synapsis and suggests a link between synaptonemal complex structural components and DNA repair.

Bolcun-Filas, E., Speed, R., Taggart, M., Grey, C., de Massy, B., Benavente, R., Cooke, HJ.

Distinct histone modifications define initiation and repair of meiotic recombination in mouse

Buard, J., Barthès, P., Grey, C. and de Massy, B_.

Repeat Length and RNA Expression Level Are Not Primary Determinants in CUG Expansion Toxicity in Drosophila Models

Le Mée, G., Ezzeddine, N., Capri, M., Aït-Ahmed, O.

Distinct Functions of MLH3 at Recombination Hot Spots in the Mouse.

Svetlanov A, Baudat F, Cohen PE, de Massy B.

Playing hide and seek with mammalian meiotic crossover hotspots.

Buard, J., De Massy, B.

Characterization of Spo11-dependent and independent phospho-H2AX foci during meiotic prophase I in the male mouse

Chicheportiche A, Bernardino-Sgherri J, de Massy B, Dutrillaux B.

Cis- and Trans-Acting Elements Regulate the Mouse Psmb9 Meiotic Recombination Hotspot.

Baudat, F., de Massy, B

Regulating double-stranded DNA break repair towards crossover or non-crossover during mammalian meiosis

Baudat, F., de Massy, B.

Oligomerization of EDEN-BP is required for specific mRNA deadenylation and binding.

Cosson, B., Gautier-Courteille, C., Maniey, D., Ait-Ahmed, O., Lesimple, M., Osborne, H.B., Paillard, L.

A Fast and Specific Alignment Method for Minisatellite Maps

Bérard S., Buard J. et E. Rivals.

Crossover and noncrossover pathways in mouse meiosis.

Guillon, H., Baudat, F., Grey, C., Liskay, R.M. and de Massy, B

Manipulating multiple sequence alignments via MaM and WebMaM

Alkan, C., Tuzun, E., Buard, J., Lethiec, F., Eichler, EE., Bailey JA., Sahinalp, SC.

Male cell microchimerism in normal and diseased female livers from fetal life to adulthood

Guettier, C., Sebagh, M., Buard, J., Feneux, D., Ortin-Serrano, M., Gigou, M., Tricottet, V., Reynes, M., Samuel, D., Feray, C.

The Drosophila Bruno paralogue Bru-3 specifically binds the EDEN translational repression element.

Delaunay J, Le Mée G, Ezzeddine N, Labesse G, Terzian C, Capri M, Aït-Ahmed O.

Recombination across the centromere of disjoined and non-disjoined chromosomes 21

Laurent, A. M., Li, M., Sherman, S., Roizes, G., Buard, J.,

Distribution of meiotic recombination sites

de Massy, B.

EDEN-dependent translational repression of maternal mRNAs is conserved between Xenopus and Drosophila

Ezzeddine, N., Paillard, L., Capri, M., Maniey, D., Bassez, T., Aït-Ahmed, O. and Osborne, H.B.

Instability of the human minisatellite CEB1 in rad27Delta and dna2-1 replication-deficient yeast cells.

Lopes J., Debrauwere H., Buard J., Nicolas A.

Evolutionary fate of an unstable human minisatellite deduced from sperm-mutation spectra of individual alleles.

Buard J., Brenner C., Jeffreys A.J.

An initiation site for meiotic crossing-over and gene conversion in the mouse

Guillon H. and de Massy B.

Identification and characterization of an Spo11 homolog in the mouse

Metzler-Guillemain, C. et de Massy B.

Somatic versus germline mutation processes at minisatellite CEB1 (D2S90) in humans and transgenic mice

Buard J., Collick A., Brown J. and Jeffreys, A.J.

Meiotic recombination and flanking marker exchange at the highly unstable human minisatellite CEB1 (D2S90)

Buard, J., Shone, A.C. and Jeffreys, A.J.

Mécanisme d’instabilité des minisatellites.

Debrauwere H., Nicolas A., Vergnaud G., Buard J., Tessier J. et Aubert D.

Influence of allele lineage on the role of the insulin minisatellite in susceptibility to type 1 diabetes.

Stead JD, Buard J, Todd JA, Jeffreys AJ.

The essential role of yeast topoisomerase III in meiosis depends on recombination.

Gangloff, S., De Massy, B., Lane, A., Rothstein, R. and Fabre, F.

Meiotic instability of human minisatellite CEB1 in yeast requires DNA double-strand breaks.

Debrauwere H, Buard J, Tessier J, Aubert D, Vergnaud G, Nicolas A.

Implication of a 5'coding sequence in targeting maternal mRNA to the Drosophila oocyte.

Capri, M., Santoni, M.J., Thomas-Delaage, M. and Aït-Ahmed, O.

Mitotic recombination and localized DNA double-strand breaks are induced after 8-methoxy psoralen and UVA irradiation in Saccharomyces cerevisia.

Dardhalon, M., De Massy, B., Nicolas, A. and Averbeck, D.

A sequence based computational identification of Drosophila developmentally regulated TATA-less NA polymerase II promoter and its experimental validation.

Santoni, M.J., Aït-Ahmed, O. and Marilley, M.


A Testis-Specific Chaperone and the Chromatin Remodeler ISWI Mediate Repackaging of the Paternal Genome

Doyen CM1, Chalkley GE1, Voets O1, Bezstarosti K2, Demmers JA2, Moshkin YM1, Verrijzer CP3.
2015 - Cell Rep , 13, 7, 1310-1318 26549447
Service porteur : Laboratory of Molecular Virology

Anatomical and Molecular Analyses of XY Ovaries from the African Pygmy Mouse Mus minutoides

Rahmoun M, Perez J, Saunders PA, Boizet-Bonhoure B, Wilhelm D, Poulat F, Veyrunes F.
2014 - Sex Dev. , 8, 6, 356-363 25359508
Service porteur : Development and Pathology of the gonad

Maraviroc-induced decrease in circulating bacterial products is not linked to an increase in immune activation in HIV-infected individuals.

Psomas C, Lavigne JP, Barbuat C, Trabelsi S, Ghosn J, Lascoux-Combe C, Flandre P, Cuzin L, Reynes J, Autran B, Corbeau P.
2013 - Blood , 122(13):2282-3.
Service porteur : Homing, immune activation and infection

MCM8- and MCM9-Deficient Mice Reveal Gametogenesis Defects and Genome Instability Due to Impaired Homologous Recombination

Lutzmann M, Grey C, Traver S, Ganier O, Maya-Mendoza A, Ranisavljevic N, Bernex F, Nishiyama A, Montel N, Gavois E, Forichon L, de Massy B, Méchali M.
2012 - Mol. Cell , 47, 4, 523-534 22771120
Service porteur : Replication and Genome Dynamics

The regulation of competence to replicate in meiosis by Cdc6 is conserved during evolution.

Lemaitre, JM., Bocquet, S., Terret, ME., Namdar, M., Ait-Ahmed, O., Kearsey, S., Verlhac, MH., and Méchali, M.
2004 - Mol Reprod Dev. , 69, 94-100 15278909
Service porteur : Replication and Genome Dynamics

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NORE Alexandre
NORE Alexandre
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VELASCO Cecilia Oliver
VELASCO Cecilia Oliver
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COUGNENC Pierre-baptiste
COUGNENC Pierre-baptiste
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PALOC Pierre-antoine
PALOC Pierre-antoine
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