Functional organization of protein determinants of meiotic DNA break hotspots

Abstract During Schizosaccharomyces pombe meiotic prophase, homologous chromosomes are co-aligned by linear elements (LinEs) analogous to the axial elements of the synaptonemal complex (SC) in other organisms. LinE proteins also promote the formation of meiotic DNA double-strand breaks (DSBs), the p...

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Autores principales:	Lijuan Ma, Kyle R. Fowler, Cristina Martín-Castellanos, Gerald R. Smith
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fdf1defa6ef34b55a79dabb06be7e905
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spelling	oai:doaj.org-article:fdf1defa6ef34b55a79dabb06be7e9052021-12-02T12:32:18ZFunctional organization of protein determinants of meiotic DNA break hotspots10.1038/s41598-017-00742-32045-2322https://doaj.org/article/fdf1defa6ef34b55a79dabb06be7e9052017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00742-3https://doaj.org/toc/2045-2322Abstract During Schizosaccharomyces pombe meiotic prophase, homologous chromosomes are co-aligned by linear elements (LinEs) analogous to the axial elements of the synaptonemal complex (SC) in other organisms. LinE proteins also promote the formation of meiotic DNA double-strand breaks (DSBs), the precursors of cross-overs. Rec10 is required for essentially all DSBs and recombination, and three others (Rec25, Rec27, and Mug20) are protein determinants of DSB hotspots – they bind DSB hotspots with high specificity and are required for DSB formation there. These four LinE proteins co-localize in the nucleus in an interdependent way, suggesting they form a complex. We used random mutagenesis to uncover recombination-deficient missense mutants with novel properties. Some missense mutations changed essential residues conserved among Schizosaccharomyces species. DSB formation, gene conversion, and crossing-over were coordinately reduced in the mutants tested. Based on our mutant analysis, we revised the rec27 open reading frame: the new start codon is in the previously annotated first intron. Genetic and fluorescence-microscopy assays indicated that the Rec10 N- and C-terminal regions have complex interactions with Rec25. These mutants are a valuable resource to elucidate further how LinE proteins and the related SCs of other species regulate meiotic DSB formation to form crossovers crucial for meiosis.Lijuan MaKyle R. FowlerCristina Martín-CastellanosGerald R. SmithNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lijuan Ma Kyle R. Fowler Cristina Martín-Castellanos Gerald R. Smith Functional organization of protein determinants of meiotic DNA break hotspots
description	Abstract During Schizosaccharomyces pombe meiotic prophase, homologous chromosomes are co-aligned by linear elements (LinEs) analogous to the axial elements of the synaptonemal complex (SC) in other organisms. LinE proteins also promote the formation of meiotic DNA double-strand breaks (DSBs), the precursors of cross-overs. Rec10 is required for essentially all DSBs and recombination, and three others (Rec25, Rec27, and Mug20) are protein determinants of DSB hotspots – they bind DSB hotspots with high specificity and are required for DSB formation there. These four LinE proteins co-localize in the nucleus in an interdependent way, suggesting they form a complex. We used random mutagenesis to uncover recombination-deficient missense mutants with novel properties. Some missense mutations changed essential residues conserved among Schizosaccharomyces species. DSB formation, gene conversion, and crossing-over were coordinately reduced in the mutants tested. Based on our mutant analysis, we revised the rec27 open reading frame: the new start codon is in the previously annotated first intron. Genetic and fluorescence-microscopy assays indicated that the Rec10 N- and C-terminal regions have complex interactions with Rec25. These mutants are a valuable resource to elucidate further how LinE proteins and the related SCs of other species regulate meiotic DSB formation to form crossovers crucial for meiosis.
format	article
author	Lijuan Ma Kyle R. Fowler Cristina Martín-Castellanos Gerald R. Smith
author_facet	Lijuan Ma Kyle R. Fowler Cristina Martín-Castellanos Gerald R. Smith
author_sort	Lijuan Ma
title	Functional organization of protein determinants of meiotic DNA break hotspots
title_short	Functional organization of protein determinants of meiotic DNA break hotspots
title_full	Functional organization of protein determinants of meiotic DNA break hotspots
title_fullStr	Functional organization of protein determinants of meiotic DNA break hotspots
title_full_unstemmed	Functional organization of protein determinants of meiotic DNA break hotspots
title_sort	functional organization of protein determinants of meiotic dna break hotspots
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fdf1defa6ef34b55a79dabb06be7e905
work_keys_str_mv	AT lijuanma functionalorganizationofproteindeterminantsofmeioticdnabreakhotspots AT kylerfowler functionalorganizationofproteindeterminantsofmeioticdnabreakhotspots AT cristinamartincastellanos functionalorganizationofproteindeterminantsofmeioticdnabreakhotspots AT geraldrsmith functionalorganizationofproteindeterminantsofmeioticdnabreakhotspots
_version_	1718394135050715136

Functional organization of protein determinants of meiotic DNA break hotspots

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