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J Cell Sci. 2015 May 1;128(9):1800-11. doi: 10.1242/jcs.165464. Epub 2015 Mar 20.

MEI4 – a central player in the regulation of meiotic DNA double-strand break formation in the mouse.

Author information

1
Institute of Human Genetics, UPR 1142, CNRS. 141, Rue de la Cardonille, 34396 Montpellier, France.
2
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR7104 - INSERM U964, Department of Functional Genomics and Cancer, 1 rue Laurent Fries, BP10142, 67404 ILLKIRCH CEDEX, France.
3
Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
4
Department of Cell and Molecular Biology (CMB), Berzelius Väg 35, Box 285, Karolinska Institutet, S-171 77 Stockholm, Sweden.
5
Cornell University, College of Veterinary Medicine T9014A, Ithaca, NY 14853 USA.
6
Institute of Physiological Chemistry, Medical Faculty of TU Dresden, Fiedlerstrasse 42, 01307 Dresden, Germany.
7
Institute of Human Genetics, UPR 1142, CNRS. 141, Rue de la Cardonille, 34396 Montpellier, France bernard.de-massy@igh.cnrs.fr.

Abstract

The formation of programmed DNA double-strand breaks (DSBs) at the beginning of meiotic prophase marks the initiation of meiotic recombination. Meiotic DSB formation is catalyzed by SPO11 and their repair takes place on meiotic chromosome axes. The evolutionarily conserved MEI4 protein is required for meiotic DSB formation and is localized on chromosome axes. Here, we show that HORMAD1, one of the meiotic chromosome axis components, is required for MEI4 localization. Importantly, the quantitative correlation between the level of axis-associated MEI4 and DSB formation suggests that axis-associated MEI4 could be a limiting factor for DSB formation. We also show that MEI1, REC8 and RAD21L are important for proper MEI4 localization. These findings on MEI4 dynamics during meiotic prophase suggest that the association of MEI4 to chromosome axes is required for DSB formation, and that the loss of this association upon DSB repair could contribute to turning off meiotic DSB formation.

KEYWORDS:

DNA double strand break; Meiosis; Recombination; Synapsis

PMID:
25795304
PMCID:
PMC4446737
DOI:
10.1242/jcs.165464
[Indexed for MEDLINE]
Free PMC Article

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