Ensuring meiotic DNA break formation in the mouse pseudoautosomal region Journal Article

Authors: 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.
Article Title: Ensuring meiotic DNA break formation in the mouse pseudoautosomal region
Abstract: 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 segregation1,2. 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. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
Keywords: chromosome; gene expression; dna; rodent; synapsis; ultrastructure; recombination; maturation; eutheria; hyperaccumulation
Journal Title: Nature
Volume: 582
Issue: 7812
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2020-06-18
Start Page: 426
End Page: 431
Language: English
DOI: 10.1038/s41586-020-2327-4
PUBMED: 32461690
PROVIDER: scopus
PMCID: PMC7337327
Notes: Article -- Export Date: 1 July 2020 -- Source: Scopus
Citation Impact
MSK Authors
  1. Scott N Keeney
    111 Keeney
  2. Liisa Hannele Kauppi
    10 Kauppi
  3. Maria Jasin
    223 Jasin
  4. Mehmet Erman Karasu
    5 Karasu
  5. Tao Li
    1 Li