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separation of dna replication from the assembly of break-competent meiotic chromosomes hannah g. blitzblau 1,2 , clara s. chan 1 , andreas hochwagen 2,3 , stephen p. bell 1 * 1department of biology, howard hughes medical institute, massachusetts institute of technology, cambridge, massachusetts, united states of america,2whitehead institute for biomedical research, nine cambridge center, cambridge, massachusetts, united states of america, 3department of biology, new york university, new york, new york, united states of america abstract the meiotic cell division reduces the chromosome number from diploid to haploid to form gametes for sexual reproduction. although much progress has been made in understanding meiotic recombination and the two meiotic divisions, the processes leading up to recombination, including the prolonged pre-meiotic s phase (meis) and the assembly of meiotic chromosome axes, remain poorly defined. we have used genome-wide approaches insaccharomyces cerevisiaeto measure the kinetics of pre-meiotic dna replication and to investigate the interdependencies between replication and axis formation. we found that replication initiation was delayed for a large number of origins in meis compared to mitosis and that meiotic cells were far more sensitive to replication inhibition, most likely due to the starvation conditions required for meiotic induction. moreover, replication initiation was delayed even in the absence of chromosome axes, indicating replication timing is independent of the process of axis assembly. finally, we found that cells were able to install axis components and initiate recombination on unreplicated dna. thus, although pre-meiotic dna replication and meiotic chromosome axis formation occur concurrently, they are not strictly coupled. the functional separation of these processes reveals a modular method of building meiotic chromosomes and predicts that any crosstalk between these modules must occur through superimposed regulatory mechanisms. citation:blitzblau hg, chan cs, hochwagen a, bell sp (2012) separation of dna replication from the assembly of break-competent meiotic chromosomes. plos genet 8(5): e1002643. doi:10.1371/journal.pgen.1002643 editor:r. scott hawley, stowers institute for medical research, united states of america receiveddecember 20, 2011;acceptedfebruary 17, 2012;publishedmay 17, 2012 copyright:2012 blitzblau et al. this is an open-access article distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. funding:spb is an investigator of the howard hughes medical institute. hgb was supported by a predoctoral fellowship from the howard hughes medical institute. this work was supported by the nih (gm088248 to ah, www.nigms.nih.gov) and the howard hughes medical institute (hhmi.org). the funders hadno role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. competing interests:the authors have declared that no competing interests exist. * e-mail: spbell@mit.edu
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