title: Temporospatial coordination of meiotic DNA replication and recombination via DDK recruitment to replisomes.
abstract: It has been long appreciated that, during meiosis, DNA replication is coordinated with the subsequent formation of the double-strand breaks (DSBs) that initiate recombination, but a mechanistic understanding of this process was elusive. We now show that, in yeast, the replisome-associated components Tof1 and Csm3 physically associate with the Dbf4-dependent Cdc7 kinase (DDK) and recruit it to the replisome, where it phosphorylates the DSB-promoting factor Mer2 in the wake of the replication fork, synchronizing replication with an early prerequisite for DSB formation. Recruiting regulatory kinases to replisomes may be a general mechanism to ensure spatial and temporal coordination of replication with other chromosomal processes.
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: Hajime
authors.initials: H
authors.lastname: Murakami
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: s-keeney@ski.mskcc.org.
authors.forename: Scott
authors.initials: S
authors.lastname: Keeney
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism; D008540:Meiosis; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D045522:Recombinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: C474335:CSM1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C088096:Dbf4 protein, S cerevisiae; D009687:Nuclear Proteins; C071054:REC107 protein, S cerevisiae; C080622:REC114 protein, S cerevisiae; D045522:Recombinases; D029701:Saccharomyces cerevisiae Proteins; C119636:TOF1 protein, S cerevisiae; C489404:CDC7 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases