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 - Funding Information:
We would like to thank Antony Oliver, Mohan Rajasekaran, Matthew Day, and Raquel Arribas for help with protein purification and the fluorescence polarization assay. We thank Shirleen Roeder, Kirsten Benjamin, Michael Lichten, Angelika Amon, and Bruce Stillman for strains/antibodies, and Katsuki Johzuka for sharing resources for Southern blotting. We would also like to extend our gratitude to Antony Carr for encouragement and support. This work was supported by grants from the Biotechnology and Biological Sciences Research Council (BB/I009159/1) and Japan Society for the Promotion of Science (JSPS; 16H07422) to H.T.; a Medical Research Council doctoral studentship to B.A.; a Grant-in-Aid for Scientific Research on Innovative Areas from JSPS (15H059749) to H.I.; a Grant-in-Aid for Young Scientists (A) from JSPS (16H06160) to Y.M.; and NIH grant GM111715 to A.H.
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
VL - 36
SP - 2488
EP - 2509
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 17
ER -