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Elife. 2017 Jan 4;6. pii: e21900. doi: 10.7554/eLife.21900.

Concerted action of the MutLβ heterodimer and Mer3 helicase regulates the global extent of meiotic gene conversion.

Author information

1
Institut Curie, PSL Research University, CNRS UMR3664, Paris, France.
2
Université Pierre et Marie Curie, Paris, France.
3
Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.
4
I2BC, iBiTec-S, CEA, CNRS UMR 9198, Université Paris-Sud, Gif-sur-Yvette, France.
5
Université Paris Sud, Orsay, France.
6
CRCM, Inserm U1068, Institut Paoli-Calmettes, Aix-Marseille Université UM105, CNRS UMR7258, Marseille, France.
7
Musée de l'Homme, CNRS UMR 7206, Paris, France.
8
Institut Curie, Centre de Recherche, PSL Research University, LSMP, Paris, France.

Abstract

Gene conversions resulting from meiotic recombination are critical in shaping genome diversification and evolution. How the extent of gene conversions is regulated is unknown. Here we show that the budding yeast mismatch repair related MutLβ complex, Mlh1-Mlh2, specifically interacts with the conserved meiotic Mer3 helicase, which recruits it to recombination hotspots, independently of mismatch recognition. This recruitment is essential to limit gene conversion tract lengths genome-wide, without affecting crossover formation. Contrary to expectations, Mer3 helicase activity, proposed to extend the displacement loop (D-loop) recombination intermediate, does not influence the length of gene conversion events, revealing non-catalytical roles of Mer3. In addition, both purified Mer3 and MutLβ preferentially recognize D-loops, providing a mechanism for limiting gene conversion in vivo. These findings show that MutLβ is an integral part of a new regulatory step of meiotic recombination, which has implications to prevent rapid allele fixation and hotspot erosion in populations.

KEYWORDS:

S. cerevisiae; biochemistry; chromosomes; genes; meiosis; mismatch repair; recombination

PMID:
28051769
PMCID:
PMC5215242
DOI:
10.7554/eLife.21900
[Indexed for MEDLINE]
Free PMC Article

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