TY - JOUR
T1 - Fundamental cell cycle kinases collaborate to ensure timely destruction of the synaptonemal complex during meiosis
AU - Argunhan, Bilge
AU - Leung, Wing Kit
AU - Afshar, Negar
AU - Terentyev, Yaroslav
AU - Subramanian, Vijayalakshmi V.
AU - Murayama, Yasuto
AU - Hochwagen, Andreas
AU - Iwasaki, Hiroshi
AU - Tsubouchi, Tomomi
AU - Tsubouchi, Hideo
N1 - Publisher Copyright:
© 2017 The Authors
PY - 2017/9/1
Y1 - 2017/9/1
N2 - The synaptonemal complex (SC) is a proteinaceous macromolecular assembly that forms during meiotic prophase I and mediates adhesion of paired homologous chromosomes along their entire lengths. Although prompt disassembly of the SC during exit from prophase I is a landmark event of meiosis, the underlying mechanism regulating SC destruction has remained elusive. Here, we show that DDK (Dbf4-dependent Cdc7 kinase) is central to SC destruction. Upon exit from prophase I, Dbf4, the regulatory subunit of DDK, directly associates with and is phosphorylated by the Polo-like kinase Cdc5. In parallel, upregulated CDK1 activity also targets Dbf4. An enhanced Dbf4-Cdc5 interaction pronounced phosphorylation of Dbf4 and accelerated SC destruction, while reduced/abolished Dbf4 phosphorylation hampered destruction of SC proteins. SC destruction relieved meiotic inhibition of the ubiquitous recombinase Rad51, suggesting that the mitotic recombination machinery is reactivated following prophase I exit to repair any persisting meiotic DNA double-strand breaks. Taken together, we propose that the concerted action of DDK, Polo-like kinase, and CDK1 promotes efficient SC destruction at the end of prophase I to ensure faithful inheritance of the genome.
AB - The synaptonemal complex (SC) is a proteinaceous macromolecular assembly that forms during meiotic prophase I and mediates adhesion of paired homologous chromosomes along their entire lengths. Although prompt disassembly of the SC during exit from prophase I is a landmark event of meiosis, the underlying mechanism regulating SC destruction has remained elusive. Here, we show that DDK (Dbf4-dependent Cdc7 kinase) is central to SC destruction. Upon exit from prophase I, Dbf4, the regulatory subunit of DDK, directly associates with and is phosphorylated by the Polo-like kinase Cdc5. In parallel, upregulated CDK1 activity also targets Dbf4. An enhanced Dbf4-Cdc5 interaction pronounced phosphorylation of Dbf4 and accelerated SC destruction, while reduced/abolished Dbf4 phosphorylation hampered destruction of SC proteins. SC destruction relieved meiotic inhibition of the ubiquitous recombinase Rad51, suggesting that the mitotic recombination machinery is reactivated following prophase I exit to repair any persisting meiotic DNA double-strand breaks. Taken together, we propose that the concerted action of DDK, Polo-like kinase, and CDK1 promotes efficient SC destruction at the end of prophase I to ensure faithful inheritance of the genome.
KW - Dbf4-dependent Cdc7 kinase
KW - Polo-like kinase
KW - homologous recombination
KW - meiosis
KW - synaptonemal complex
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U2 - 10.15252/embj.201695895
DO - 10.15252/embj.201695895
M3 - Article
C2 - 28694245
AN - SCOPUS:85022337792
SN - 0261-4189
VL - 36
SP - 2488
EP - 2509
JO - EMBO Journal
JF - EMBO Journal
IS - 17
ER -