Evidence that MEK1 positively promotes interhomologue double-strand break repair.
During meiosis there is an imperative to create sufficient crossovers for homologue segregation. This can be achieved during repair of programmed DNA double-strand breaks (DSBs), which are biased towards using a homologue rather than sister chromatid as a repair template. Various proteins contribute to this bias, one of which is a meiosis specific kinase Mek1. It has been proposed that Mek1 establishes the bias by creating a barrier to sister chromatid repair, as distinct from enforcing strand invasion with the homologue. We looked for evidence that Mek1 positively stimulates strand invasion of the homologue. This was done by analysing repair of DSBs induced by the VMA1-derived endonuclease (VDE) and flanked by directly repeated sequences that can be used for intrachromatid single-strand annealing (SSA). SSA competes with interhomologue strand invasion significantly more successfully when Mek1 function is lost. We suggest the increase in intrachromosomal SSA reflects an opportunistic default repair pathway due to loss of a MEK1 stimulated bias for strand invasion of the homologous chromosome. Making use of an inhibitor sensitive mek1-as1 allele, we found that Mek1 function influences the repair pathway throughout the first4-5 h of meiosis. Perhaps reflecting a particular need to create bias for successful interhomologue events before chromosome pairing is complete.
Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield S10 2TN, UK.
Yaroslav
Y
Terentyev
Rebecca
R
Johnson
Matthew J
MJ
Neale
Muhammad
M
Khisroon
Anna
A
Bishop-Bailey
Alastair S H
AS
Goldman
D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D005785:Gene Conversion; D048369:MAP Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism*; D008540:Meiosis; D009154:Mutation; D006180:Proton-Translocating ATPases / Q000378:metabolism; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013172:Spores, Fungal / Q000201:enzymology
D029701:Saccharomyces cerevisiae Proteins; D048369:MAP Kinase Kinase 1; D006180:Proton-Translocating ATPases; C081687:VMA1 protein, S cerevisiae