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Proc Natl Acad Sci U S A. 2011 Dec 13;108(50):20036-41. doi: 10.1073/pnas.1117937108. Epub 2011 Nov 28.

Meiotic double-strand breaks occur once per pair of (sister) chromatids and, via Mec1/ATR and Tel1/ATM, once per quartet of chromatids.

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  • 1Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.

Erratum in

  • Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1353.


Meiotic recombination initiates via programmed double-strand breaks (DSBs). We investigate whether, at a given initiation site, DSBs occur independently among the four available chromatids. For a single DSB "hot spot", the proportions of nuclei exhibiting zero, one, or two (or more) observable events were defined by tetrad analysis and compared with those predicted by different DSB distribution scenarios. Wild-type patterns are incompatible with independent distribution of DSBs among the four chromatids. In most or all nuclei, DSBs occur one-per-pair of chromatids, presumptively sisters. In many nuclei, only one DSB occurs per four chromatids, confirming the existence of trans inhibition where a DSB on one chromosome interactively inhibits DSB formation on the partner chromosome. Several mutants exhibit only a one-per-pair constraint, a phenotype we propose to imply loss of trans inhibition. Signal transduction kinases Mec1 (ATR) and Tel1 (ATM) exhibit this phenotype and thus could be mediators of this effect. Spreading trans inhibition can explain even spacing of total recombinational interactions and implies that establishment of interhomolog interactions and DSB formation are homeostatic processes. The two types of constraints on DSB formation provide two different safeguards against recombination failure during meiosis.

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