Mnd1 is required for meiotic interhomolog repair.
BACKGROUND
While double-strand break (DSB) repair is vital to the survival of cells during both meiosis and mitosis, the preferred mechanism of repair differs drastically between the two types of cell cycle. Thus, during meiosis, it is the homologous chromosome rather than the sister chromatid that is used as a repair template.


RESULTS
Cells attempting to undergo meiosis in the absence of Mnd1 arrest in prophase I due to the activation of the Mec1 DNA-damage checkpoint accumulating hyperresected DSBs and aberrant synapsis. Sporulation of mnd1Delta strains can be restored by deleting RED1 or HOP1, which permits repair of DSBs by using the sister chromatid as a repair template. Mnd1 localizes to chromatin as foci independently of DSB formation, axial element (AE) formation, and synaptonemal complex (SC) formation and does not colocalize with Rad51. Mnd1 does not preferentially associate with hotspots of recombination.


CONCLUSIONS
Our results suggest that Mnd1 acts specifically to promote DSB repair by using the homologous chromosome as a repair template. The presence of Rec8, Red1, or Hop1 renders Mnd1 indispensable for DNA repair, presumably through the establishment of interhomolog (IH) bias. Localization studies suggest that Mnd1 carries out this function without being specifically recruited to the sites of DNA repair. We propose a model in which Mnd1 facilitates chromatin accessibility, which is required to allow strand invasion in meiotic chromatin.
Zierhut
Christian
C
Max F. Perutz Laboratories, Cell Biology and Genetics, Institute of Botany, University of Vienna, Rennweg 14, A-1030, Vienna, Austria.
Berlinger
Marc
M
Rupp
Christian
C
Shinohara
Akira
A
Klein
Franz
F
D015139:Blotting, Southern; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015825:Chromosomes, Fungal / Q000502:physiology*; D004249:DNA Damage / Q000502:physiology*; D017931:DNA Primers; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008540:Meiosis / Q000502:physiology*; D008954:Models, Biological; D010750:Phosphoproteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D000097722:Cohesins
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D017931:DNA Primers; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C086672:HOP1 protein, S cerevisiae; C454441:MND1 protein, S cerevisiae; C086673:RED1 protein, S cerevisiae; C077081:REC8 protein, S pombe; D000097722:Cohesins