real-time-observation-dna-strand-exchange-reaction-mediated

Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51

The DNA strand exchange reaction mediated by Rad51 is a critical step of homologous recombination. In this reaction, Rad51 forms a nucleoprotein filament ...

Tokyo Institute of Technology

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.

Fundamental cell cycle kinases collaborate to ensure timely destruction of the synaptonemal complex during meiosis.

The meiotic cell cycle provides a unique model to study the relationship between recombinational DNA repair and the cell cycle, since homologous recombination, induced by programmed DNA double-strand breaks (DSBs), is integrated as an essential step during meiosis. The pachytene checkpoint, which is situated towards the end of meiotic prophase I, coordinates homologous recombination and cell cycle progression, similar to the DNA damage checkpoint mechanisms operating in vegetative cells. However, there are a number of features unique to meiosis, making the system optimized for the purpose of meiosis. Our recent work highlights the involvement of three major cell cycle kinases, Dbf4-dependent Cdc7 kinase, Polo kinase and CDK, in coordinating homologous recombination and the meiotic cell cycle. In this review, we will discuss the unique interplay between meiotic cell cycle control and homologous recombination during meiosis I.

Bilge Argunhan

Cell Biology Center,
Institute of Innovative Research,
Cell Biology Center, Institute of Innovative Research

Tokyo Institute of Technology

Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51

Bilge Argunhan

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Tokyo Institute of Technology

Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51

Cell Biology Center,
Institute of Innovative Research,
Cell Biology Center, Institute of Innovative Research