Coordinating Replication with Transcription

Achar, Yathish Jagadheesh; Foiani, Marco

doi:10.1007/978-981-10-6955-0_20

Cited by 14 publications

(11 citation statements)

References 194 publications

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“…It results in the deposition of ␥H2A at the tDNA, which is necessary for fork recovery from the pause/stall (20,29,(86)(87)(88)(89)(90). Rrm3 and topoisomerases play a role in the recovery of stalled replication forks at protein-bound sites in the genome, such as tDNAs (88,91,92). Therefore, we analyzed the effects of these mutants on HML-HMR long-range association.…”

Section: Resultsmentioning

confidence: 99%

tRNA Genes Affect Chromosome Structure and Function via Local Effects

Hamdani

Hsieh

Rando

et al. 2019

Molecular and Cellular Biology

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The genome is packaged and organized in an ordered, nonrandom manner, and specific chromatin segments contact nuclear substructures to mediate this organization. tRNA genes (tDNAs) are binding sites for transcription factors and architectural proteins and are thought to play an important role in the organization of the genome. In this study, we investigate the roles of tDNAs in genomic organization and chromosome function by editing a chromosome so that it lacked any tDNAs. Surprisingly our analyses of this tDNA-less chromosome show that loss of tDNAs does not grossly affect chromatin architecture or chromosome tethering and mobility. However, loss of tDNAs affects local nucleosome positioning and the binding of SMC proteins at these loci. The absence of tDNAs also leads to changes in centromere clustering and a reduction in the frequency of long-range HML-HMR heterochromatin clustering with concomitant effects on gene silencing. We propose that the tDNAs primarily affect local chromatin structure, which results in effects on long-range chromosome architecture.

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Section: Resultsmentioning

confidence: 99%

tRNA Genes Affect Chromosome Structure and Function via Local Effects

Hamdani

Hsieh

Rando

et al. 2019

Molecular and Cellular Biology

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“…Foiani, 449 2017; Azvolinsky et al, 2009; D'Ambrosio et al, 2008; Deshpande and Newlon, 1996; 450 Kirkland and Kamakaka, 2013; Lengronne et al, 2004; Szilard et al, 2010). Rrm3 and 451topoisomerases play a role in the recovery of stalled replication forks at protein bound 452 sites in the genome such as tDNAs(Achar and Foiani, 2017;Azvolinsky et al, 2006; 453 Ivessa et al, 2003). Therefore we analyzed the effect of these mutants on HML-HMR 454 long-range association.…”

mentioning

confidence: 99%

Transfer RNA Genes Affect Chromosome Structure and Function via Local Effects

Hamdani¹,

Dhillon²,

Hsieh³

et al. 2018

Preprint

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The genome is packaged and organized in an ordered, non-random manner and specific chromatin segments contact nuclear substructures to mediate this organization. While transfer RNA genes (tDNAs) are essential for the generation of tRNAs, these loci are also binding sites for transcription factors and architectural proteins and are thought to play an important role in the organization of the genome. In this study, we investigate the role of tDNAs in genomic organization and chromosome function by editing a chromosome so that it lacks any tDNAs. Surprisingly our analyses of this tDNA-less chromosome show that loss of tDNAs does not grossly affect chromosome folding or chromosome tethering. However, loss of tDNAs affects local nucleosome positioning and the binding of SMC proteins at these loci. The absence of tDNAs also leads to changes in centromere clustering and a reduction in the frequency of long range HML-HMR heterochromatin clustering. We propose that the tDNAs primarily affect local chromatin structure that result in effects on long-range chromosome architecture.

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“…Unexpectedly, SSRP1-mediated MBT delay and accelerated development due to stimulation of DNA replication does not interfere with active transcription, as shown by the absence of DNA double strand breaks, which can occur when DNA replication forks collide head on with transcription units 33 . Intriguingly, SSRP1 is enriched at transcription start sites (TSSs) 15 whereas histone H1 is selective depleted from these 41 .…”

Section: Discussionmentioning

confidence: 98%

“…7). As replication origins might interfere with transcription events inducing DNA damage as result of DNA transcription and DNA replication conflicts 33 , we monitored the occurrence of DNA double strand breaks by measuring the levels of H2AX phosphorylation 34 in embryos with accelerated development. Although phospho-H2AX levels could be detected in tissue sections of embryos subjected to mild ionizing radiation, SSRP1 did not induce measurable levels of H2AX phosphorylation ( Supplementary Fig.…”

Section: Ssrp1 Accelerates Development By Increasing Cell Cycle Speedmentioning

confidence: 99%

SSRP1-mediated histone H1 eviction promotes replication origin assembly and accelerated development

et al. 2020

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In several metazoans, the number of active replication origins in embryonic nuclei is higher than in somatic ones, ensuring rapid genome duplication during synchronous embryonic cell divisions. High replication origin density can be restored by somatic nuclear reprogramming. However, mechanisms underlying high replication origin density formation coupled to rapid cell cycles are poorly understood. Here, using Xenopus laevis, we show that SSRP1 stimulates replication origin assembly on somatic chromatin by promoting eviction of histone H1 through its N-terminal domain. Histone H1 removal derepresses ORC and MCM chromatin binding, allowing efficient replication origin assembly. SSRP1 protein decays at mid-blastula transition (MBT) when asynchronous somatic cell cycles start. Increasing levels of SSRP1 delay MBT and, surprisingly, accelerate post-MBT cell cycle speed and embryo development. These findings identify a major epigenetic mechanism regulating DNA replication and directly linking replication origin assembly, cell cycle duration and embryo development in vertebrates.

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Coordinating Replication with Transcription

Cited by 14 publications

References 194 publications

tRNA Genes Affect Chromosome Structure and Function via Local Effects

tRNA Genes Affect Chromosome Structure and Function via Local Effects

Transfer RNA Genes Affect Chromosome Structure and Function via Local Effects

SSRP1-mediated histone H1 eviction promotes replication origin assembly and accelerated development

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