Abstract
Hydroxyurea (HU), an inhibitor of ribonucleotide reductase, prevents cells from progressing through S phase by depletion of deoxyribonucleoside triphosphates. Concurrently, disruption of DNA replication leads to double-strand DNA breaks. In root meristems of Vicia faba, HU triggers cell cycle arrest (preferentially in G1/S phase) and changes an overall metabolism by global activation of transcription both in the nucleoplasmic and nucleolar regions. High level of transcription is accompanied by an increase in the content of RNA polymerase II large subunit (POLR2A). Changes in transcription activation and POLR2A content correlate with posttranslational modifications of histones that play a role in opening up chromatin for transcription. Increase in the level of H4 Lys5 acetylation indicates that global activation of transcription following HU treatment depends on histone modifications.
Highlights
Cell cycle transitions throughout interphase and mitosis are regulated by sophisticated metabolic pathways comprising diverse proteins
The results presented in this work indicate that in root meristems of Vicia faba, HU leads to cell cycle arrest and triggers changes in cellular metabolic state manifested by global transcription activation correlated with an increased content of RNA polymerase II and histone H4 Lys5 acetylation (H4K5Ac)
Jasencakova et al (2000) link H4 Lys5 acetylation in V. faba with replication rather than transcription. These data seem to be in contrast to the results presented in our paper, Belyaev et al (1997) clearly show that unlike euchromatin, late-replicating heterochromatic regions of V. faba metaphase chromosomes are hypoacetylated, and only roots treated with trichostatin A display acetylation of heterochromatic regions in metaphase chromosomes
Summary
Cell cycle transitions throughout interphase and mitosis are regulated by sophisticated metabolic pathways comprising diverse proteins. Inhibition of RNR activity prevents cells from progressing through S phase by enhanced production of replication intermediates, including long ssDNA regions and inappropriate processing of the reversed forks, which leads to dsDNA breaks (DSB; Sogo et al 2002). HU triggers changes in an overall cellular metabolism resulting in an enhanced expression of diverse genes, e.g., γ-globin (Watanapokasin et al 2006), adult β-globin in HeLA cells (Zhang et al 2001), or SMN2 (survival motor neuron) in lymphoblastoid cell lines (Grzeschik et al 2005). The results presented in this work indicate that in root meristems of Vicia faba, HU leads to cell cycle arrest and triggers changes in cellular metabolic state manifested by global transcription activation correlated with an increased content of RNA polymerase II and histone H4 Lys acetylation (H4K5Ac)
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