Meiotic recombination is required for correct segregation of chromosomes to gametes and to generate genetic diversity. In mice and humans, DNA double-strand breaks (DSBs) are initiated by SPO11 at recombination hotspots activated by PRDM9-catalyzed histone modifications on open chromatin. However, the DSB-initiating and repair proteins are associated with a linear proteinaceous scaffold called the chromosome axis, the core of which is composed of cohesin proteins. STAG3 is a stromalin subunit common to all meiosis-specific cohesin complexes. Mutations of meiotic cohesin proteins, especially STAG3, perturb both axis formation and recombination in the mouse, prompting determination of how the processes are mechanistically related. Protein interaction and genetic analyses revealed that PRDM9 interacts with STAG3 and REC8 in cooperative relationships that promote normal levels of meiotic DSBs at recombination hotspots in spermatocytes. The efficacy of the Prdm9-Stag3 genetic interaction in promoting DSB formation depends on PRDM9-mediated histone methyltransferase activity. Moreover, STAG3 deficiency has a major effect on DSB number even in the absence of PRDM9, showing that its role is not restricted to canonical PRDM9-activated hotspots. STAG3 and REC8 promote axis localization of the DSB-promoting proteins HORMAD1, IHO1, and MEI4, as well as SPO11 activity. These results establish that PRDM9 and axis-associated cohesin complexes together coordinate and facilitate meiotic recombination by recruiting key proteins for initiation of DSBs, thereby associating activated hotspots with DSB-initiating complexes on the axis.
Pubmed ID: 30853435 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsPortal to interactively visualize genomic data. Provides reference sequences and working draft assemblies for collection of genomes and access to ENCODE and Neanderthal projects. Includes collection of vertebrate and model organism assemblies and annotations, along with suite of tools for viewing, analyzing and downloading data.
View all literature mentionsA generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms.
View all literature mentionsThis unknown targets Rabbit IgG
View all literature mentionsThis polyclonal targets RAD21
View all literature mentionsThis polyclonal targets SMC3
View all literature mentionsThis polyclonal targets REC8
View all literature mentionsThis isotype control targets not applicable
View all literature mentionsThis unknown targets normal guinea pig IgG
View all literature mentionsThis monoclonal targets Fluorescent TrueBlot: Anti-Mouse Ig Fluorescein
View all literature mentionsThis unknown targets normal rabbit IgG
View all literature mentionsThis monoclonal targets beta-Tubulin
View all literature mentionsThis unknown targets Goat Mouse IgG (H L)-HRP Conjugate
View all literature mentionsThis polyclonal targets H3K4me3
View all literature mentionsThis polyclonal targets Guinea Pig IgG
View all literature mentionsThis polyclonal targets Guinea pig
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets Mouse IgG (H+L)
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Guinea Pig IgG (H+L)
View all literature mentionsThis unknown targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets HORMAD1
View all literature mentionsThis monoclonal targets Histone H2A.X pSer139
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets Stra8
View all literature mentionsThis monoclonal targets SCP-3 (D-1)
View all literature mentionsThis monoclonal targets Human Histone H3
View all literature mentions