Regulation of meiotic recombination via Mek1-mediated Rad54 phosphorylation.
A preference for homologs over sister chromatids in homologous recombination is a fundamental difference in meiotic versus mitotic cells. In budding yeast, the bias for interhomolog recombination in meiosis requires the Dmc1 recombinase and the meiosis-specific kinase Mek1, which suppresses engagement of sister chromatids by the mitotic recombinase Rad51. Here, a combination of proteomic, biochemical, and genetic approaches has identified an additional role for Mek1 in inhibiting the activity of the Rad51 recombinase through phosphorylation of its binding partner, Rad54. Rad54 phosphorylation of threonine 132 attenuates complex formation with Rad51, and a negative charge at this position reduces Rad51 function in vitro and in vivo. Thus, Mek1 phosphorylation provides a dynamic means of controlling recombination partner choice in meiosis in two ways: (1) it reduces Rad51 activity through inhibition of Rad51/Rad54 complex formation, and (2) it suppresses Rad51-mediated strand invasion of sister chromatids via a Rad54-independent mechanism.
Niu
Hengyao
H
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, USA.
Wan
Lihong
L
Busygina
Valeria
V
Kwon
YoungHo
Y
Allen
Jasmina A
JA
Li
Xue
X
Kunz
Ryan C
RC
Kubota
Kazuishi
K
Wang
Beatrice
B
Sung
Patrick
P
Shokat
Kevan M
KM
Gygi
Steven P
SP
Hollingsworth
Nancy M
NM
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D053903:DNA Breaks, Double-Stranded; D004265:DNA Helicases; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D048369:MAP Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism*; D013058:Mass Spectrometry; D008540:Meiosis; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013172:Spores, Fungal / Q000235:genetics; D013912:Threonine / Q000378:metabolism
D018797:Cell Cycle Proteins; C513033:DMC1 protein, S cerevisiae; D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D013912:Threonine; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D048369:MAP Kinase Kinase 1; C495151:RAD51 protein, S cerevisiae; D051135:Rad51 Recombinase; C075468:RAD54 protein, S cerevisiae; D004265:DNA Helicases; D045643:DNA Repair Enzymes