Suppression of genetic recombination in the pseudoautosomal region and at subtelomeres in mice with a hypomorphic Spo11 allele.

Fatima Smagulova; Kevin Brick; Yongmei Pu; Uttara Sengupta; Daniel Camerini-Otero; Galina Petukhova

doi:10.1186/1471-2164-14-493

Suppression of genetic recombination in the pseudoautosomal region and at subtelomeres in mice with a hypomorphic Spo11 allele.

Fatima Smagulova ^{1, 2} Kevin Brick ³ Yongmei Pu ¹ Uttara Sengupta ¹ Daniel Camerini-Otero ³ Galina Petukhova ^{1, *}

* Auteur correspondant

1 Department of Biochemistry and Molecular Biology

2 Irset - Institut de recherche, santé, environnement et travail

3 Genetics and Biochemistry Branch

Abstract : BACKGROUND: Homologous recombination is the key process that generates genetic diversity and drives evolution. SPO11 protein triggers recombination by introducing DNA double stranded breaks at discreet areas of the genome called recombination hotspots. The hotspot locations are largely determined by the DNA binding specificity of the PRDM9 protein in human, mice and most other mammals. In budding yeast Saccharomyces cerevisae, which lacks a Prdm9 gene, meiotic breaks are formed opportunistically in the regions of accessible chromatin, primarily at gene promoters. The genome-wide distribution of hotspots in this organism can be altered by tethering Spo11 protein to Gal4 recognition sequences in the strain expressing Spo11 attached to the DNA binding domain of the Gal4 transcription factor. To establish whether similar re-targeting of meiotic breaks can be achieved in PRDM9-containing organisms we have generated a Gal4BD-Spo11 mouse that expresses SPO11 protein joined to the DNA binding domain of yeast Gal4. RESULTS: We have mapped the genome-wide distribution of the recombination initiation sites in the Gal4BD-Spo11 mice. More than two hundred of the hotspots in these mice were novel and were likely defined by Gal4BD, as the Gal4 consensus motif was clustered around the centers in these hotspots. Surprisingly, meiotic DNA breaks in the Gal4BD-Spo11 mice were significantly depleted near the ends of chromosomes. The effect is particularly striking at the pseudoautosomal region of the X and Y chromosomes -- normally the hottest region in the genome. CONCLUSIONS: Our data suggest that specific, yet-unidentified factors influence the initiation of meiotic recombination at subtelomeric chromosomal regions.

Keywords : Homologous recombination Recombination hotspots SPO11 Subtelomeres Double stranded DNA breaks

Type de document :

Article dans une revue

BMC Genomics, BioMed Central, 2013, 14 (1), pp.493. 〈10.1186/1471-2164-14-493〉

Domaine :

Sciences du Vivant [q-bio] / Biochimie, Biologie Moléculaire / Génomique, Transcriptomique et Protéomique [q-bio.GN]

Liste complète des métadonnées

http://www.hal.inserm.fr/inserm-00849779
Contributeur : Ed. Bmc <>
Soumis le : jeudi 1 août 2013 - 01:09:48
Dernière modification le : mercredi 18 juillet 2018 - 20:02:02
Document(s) archivé(s) le : lundi 4 novembre 2013 - 17:22:52

Suppression of genetic recombination in the pseudoautosomal region and at subtelomeres in mice with a hypomorphic Spo11 allele.

Fichiers

Identifiants

Collections

Citation

Exporter

Métriques

359

257

Contact

Suppression of genetic recombination in the pseudoautosomal region and at subtelomeres in mice with a hypomorphic Spo11 allele.

Fichiers

Identifiants

Collections

Citation

Exporter

Partager

Métriques

359

257

Contact