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

BMC Genomics

Research Article

Yongmei Pu¹  Galina V Petukhova¹  Uttara Sengupta²  Fatima Smagulova³  Kevin Brick⁴  R Daniel Camerini-Otero⁴ 

[1] Department of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA;Department of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA;Center for Investigative Proteomics, Northwick Park Institute for Medical Research, Northwick Park & St Mark’s Hospital, Middlesex HA1 3UJ, Harrow, England, UK;Department of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA;Inserm UMR1085-Irset 263, ave du Général Leclerc, 35042, Rennes, France;Genetics and Biochemistry Branch, National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, MD, USA;

关键词: Homologous recombination;    Recombination hotspots;    SPO11;    Subtelomeres;    Double stranded DNA breaks;   

DOI  :  10.1186/1471-2164-14-493

 received in 2013-05-31, accepted in 2013-07-10,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundHomologous 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.ResultsWe 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.ConclusionsOur data suggest that specific, yet-unidentified factors influence the initiation of meiotic recombination at subtelomeric chromosomal regions.

【 授权许可】

Unknown   
© Smagulova et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.