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

Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 11/2011; 108(50):20036-41. DOI: 10.1073/pnas.1117937108
Source: PubMed


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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    • "e as in cycling cells , and is then restored , dependent on Spo11 protein but independent of its role in DSBs ( Weiner and Kleckner 1994 ; Cha et al . 2000 ) . DSB - independent pairing interactions , before and during meiosis , may underlie ob - served trans effects of the homolog on DSB formation ( Xu and Kleckner 1995 ; Rocco and Nicolas 1996 ; Zhang et al . 2011 ) ."
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    • "Separate but related to the question of why cells make a certain number of DSBs is how they ensure that the correct number is made. The DSB-forming machinery appears to be in excess over the DSBs actually formed (Neale et al. 2005; Milman et al. 2009; Lange et al. 2011), implying the existence of feedback mechanisms that influence SPO11 activity (Joyce et al. 2011; Lange et al. 2011; Zhang et al. 2011). However, it has been unclear how such feedback is integrated with meiotic chromosome dynamics. "
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