Ensuring meiotic DNA break formation in the mouse pseudoautosomal region

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dc.contributor.author Acquaviva, Laurent
dc.contributor.author Boekhout, Michiel
dc.contributor.author Karasu, Mehmet E.
dc.contributor.author Brick, Kevin
dc.contributor.author Pratto, Florencia
dc.contributor.author Li, Tao
dc.contributor.author van Overbeek, Megan
dc.contributor.author Kauppi, Liisa
dc.contributor.author Camerini-Otero, R. Daniel
dc.contributor.author Jasin, Maria
dc.contributor.author Keeney, Scott
dc.date.accessioned 2021-02-01T13:24:01Z
dc.date.available 2021-02-01T13:24:01Z
dc.date.issued 2020-06
dc.identifier.citation Acquaviva , L , Boekhout , M , Karasu , M E , Brick , K , Pratto , F , Li , T , van Overbeek , M , Kauppi , L , Camerini-Otero , R D , Jasin , M & Keeney , S 2020 , ' Ensuring meiotic DNA break formation in the mouse pseudoautosomal region ' , Nature , vol. 582 , no. 7812 , pp. 426–431 . https://doi.org/10.1038/s41586-020-2327-4
dc.identifier.other PURE: 138999372
dc.identifier.other PURE UUID: e9d2d20c-344b-47bf-8836-9c021fdea3a5
dc.identifier.other WOS: 000535878900004
dc.identifier.uri http://hdl.handle.net/10138/325615
dc.description.abstract In mice, the pseudoautosomal region of the sex chromosomes undergoes a dynamic structural rearrangement to promote a high rate of DNA double-strand breaks and to ensure X-Y recombination. Sex chromosomes in males of most eutherian mammals share only a small homologous segment, the pseudoautosomal region (PAR), in which the formation of double-strand breaks (DSBs), pairing and crossing over must occur for correct meiotic segregation(1,2). How cells ensure that recombination occurs in the PAR is unknown. Here we present a dynamic ultrastructure of the PAR and identify controlling cis- and trans-acting factors that make the PAR the hottest segment for DSB formation in the male mouse genome. Before break formation, multiple DSB-promoting factors hyperaccumulate in the PAR, its chromosome axes elongate and the sister chromatids separate. These processes are linked to heterochromatic mo-2 minisatellite arrays, and require MEI4 and ANKRD31 proteins but not the axis components REC8 or HORMAD1. We propose that the repetitive DNA sequence of the PAR confers unique chromatin and higher-order structures that are crucial for recombination. Chromosome synapsis triggers collapse of the elongated PAR structure and, notably, oocytes can be reprogrammed to exhibit spermatocyte-like levels of DSBs in the PAR simply by delaying or preventing synapsis. Thus, the sexually dimorphic behaviour of the PAR is in part a result of kinetic differences between the sexes in a race between the maturation of the PAR structure, formation of DSBs and completion of pairing and synapsis. Our findings establish a mechanistic paradigm for the recombination of sex chromosomes during meiosis. en
dc.format.extent 25
dc.language.iso eng
dc.relation.ispartof Nature
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject CHROMOSOME AXIS
dc.subject HIGH-FREQUENCY
dc.subject RECOMBINATION
dc.subject HETEROCHROMATIN
dc.subject CONSERVATION
dc.subject INITIATION
dc.subject 3111 Biomedicine
dc.title Ensuring meiotic DNA break formation in the mouse pseudoautosomal region en
dc.type Article
dc.contributor.organization Genome Stability Group
dc.contributor.organization Faculty of Medicine
dc.contributor.organization University of Helsinki
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1038/s41586-020-2327-4
dc.relation.issn 0028-0836
dc.rights.accesslevel openAccess
dc.type.version acceptedVersion

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