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Curr Biol. 2010 Dec 7;20(23):2078-89. doi: 10.1016/j.cub.2010.10.008. Epub 2010 Oct 21.

Meiotic errors activate checkpoints that improve gamete quality without triggering apoptosis in male germ cells.

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1
Department of Molecular and Cellular Biology, Genetics Graduate Group, University of California, Davis, Davis, CA 95616, USA.

Abstract

BACKGROUND:

Meiotic checkpoints ensure the production of gametes with the correct complement and integrity of DNA; in metazoans, these pathways sense errors and transduce signals to trigger apoptosis to eliminate damaged germ cells. The extent to which checkpoints monitor and safeguard the genome differs between sexes and may contribute to the high frequency of human female meiotic errors. In the C. elegans female germline, DNA damage, chromosome asynapsis, and/or unrepaired meiotic double-strand breaks (DSBs) activate checkpoints that induce apoptosis; conversely, male germ cells do not undergo apoptosis.

RESULTS:

Here we show that the recombination checkpoint is in fact activated in male germ cells despite the lack of apoptosis. The 9-1-1 complex and the phosphatidylinositol 3-kinase-related protein kinase ATR, sensors of DNA damage, are recruited to chromatin in the presence of unrepaired meiotic DSBs in both female and male germlines. Furthermore, the checkpoint kinase CHK-1 is phosphorylated and the p53 ortholog CEP-1 induces expression of BH3-only proapoptotic proteins in germlines of both sexes under activating conditions. The core cell death machinery is expressed in female and male germlines; however, CED-3 caspase is not activated in the male germline. Although apoptosis is not triggered, checkpoint activation in males has functional consequences for gamete quality, because there is reduced viability of progeny sired by males with a checkpoint-activating defect in the absence of checkpoint function.

CONCLUSIONS:

We propose that the recombination checkpoint functions in male germ cells to promote repair of meiotic recombination intermediates, thereby improving the fidelity of chromosome transmission in the absence of apoptosis.

Comment in

PMID:
20970339
PMCID:
PMC3005853
DOI:
10.1016/j.cub.2010.10.008
[Indexed for MEDLINE]
Free PMC Article
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