Trouble in transitioning: activation of zygotic transcription can lead to DNA breakage and genome instability

Butuči, Melina; Wong, Margaret; Michael, W Matthew

doi:10.1080/21624054.2015.1115946

Cited by 2 publications

(3 citation statements)

References 21 publications

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“…Thus, nutrients serve as a signal that triggers zygotic genome activation (ZGA) in these cells. Previous work from our group has shown that, surprisingly, one manifestation of Z2/Z3 ZGA is the appearance of DNA damage (Butu ci et al, 2015a(Butu ci et al, , 2015b. Cytological markers for damage are observed shortly after hatched L1s feed, coincident with the global activation of RNAPII.…”

Section: Introductionmentioning

confidence: 80%

“…Germline ZGA Previous work from our laboratory showed that DNA breaks form in the Z2/Z3 genome concomitant with RNAPII activation and ZGA. The breaks are restricted to transcriptionally active autosomes and can only be observed on the X chromosomes if transcription is experimentally induced (Butu ci et al, 2015a(Butu ci et al, , 2015b. Thus, there is an intimate relationship between the breaks and transcriptional activation; however, the molecular mechanism in play was not known.…”

Section: Identification Of Genes Upregulated Duringmentioning

confidence: 99%

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Programmed DNA Breaks Activate the Germline Genome in Caenorhabditis elegans

et al. 2018

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In Caenorhabditis elegans, the primordial germ cells Z2 and Z3 are born during early embryogenesis and then held in a transcriptionally quiescent state where the genome is highly compacted. When hatched L1s feed, the germline genome decompacts, and RNAPII is abruptly and globally activated. A previously documented yet unexplained feature of germline genome activation in the worm is the appearance of numerous DNA breaks coincident with RNAPII transcription. Here, we show that the DNA breaks are induced by topoisomerase II and that they function to recruit the RUVB complex to chromosomes so that RUVB can decompact the chromatin. DNA break- and RUVB-mediated decompaction is required for zygotic genome activation. This work highlights the importance of global chromatin decompaction in the rapid induction of gene expression and shows that one way cells achieve global decompaction is through programmed DNA breaks.

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Section: Introductionmentioning

confidence: 80%

Section: Identification Of Genes Upregulated Duringmentioning

confidence: 99%

Programmed DNA Breaks Activate the Germline Genome in Caenorhabditis elegans

et al. 2018

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“…These findings indicate striking plasticity in establishing the germ cell fate among clades and raise the prospect that transcriptional delay is not essential for PGC formation. Interestingly, massive transcriptional activation has been previously shown to cause double-strand break (DSB) in the embryonic germline ( Butuči et al., 2015 ). Therefore, we speculate that zebrafish PGCs may experience a milder transition from a non-transcribing to a transcribing state while being less exposed to DNA damage.…”

Section: Discussionmentioning

confidence: 99%