Abstract
BackgroundDeproteinized DNA from eukaryotic and prokaryotic cells still contains a low-molecular weight peptidic fraction which can be dissociated by alkalinization of the medium. This fraction inhibits RNA transcription and tumor cell growth. Removal from DNA of normal cells causes amplification of DNA template activity. This effect is lower or absent in several cancer cell lines. Likewise, the amount of active peptides in cancer cell DNA extracts is lower than in DNA preparation of the corresponding normal cells. Such evidence, and their ubiquitous presence, suggests that they are a regulatory, conserved factor involved in the control of normal cell growth and gene expression.ResultsWe report that peptides extracted from wheat bud chromatin induce growth inhibition, G2 arrest and caspase-dependent apoptosis in HeLa cells. The growth rate is decreased in cells treated during the S phase only and it is accompanied by DNA damage and DNA synthesis inhibition. In G2 cells, this treatment induces inactivation of the CDK1-cyclin B1 complex and an increase of active chk1 kinase expression.ConclusionThe data indicate that the chromatin peptidic pool inhibits HeLa cell growth by causing defective DNA replication which, in turn, arrests cell cycle progression to mitosis via G2 checkpoint pathway activation.
Highlights
Deproteinized DNA from eukaryotic and prokaryotic cells still contains a lowmolecular weight peptidic fraction which can be dissociated by alkalinization of the medium
The peptide fraction inhibits the proliferation of HeLa cells in a concentration and time dependent manner
Effect of chromatin peptides on cell cycle progression To determine more precisely how the chromatin peptide fraction inhibits HeLa cell proliferation, we investigated whether the apoptotic process was accompanied by a cell cycle perturbation
Summary
Deproteinized DNA from eukaryotic and prokaryotic cells still contains a lowmolecular weight peptidic fraction which can be dissociated by alkalinization of the medium. It has previously been reported that these peptides inhibit RNA transcription in cells and in vitro reconstituted systems with prokaryotic and eukaryotic RNA polymerase [10,11], and that they stabilize the structure of double-stranded DNA, increasing its melting point [12] When they are removed by alkaline buffer from DNA of normal cells DNA template capacity is enhanced [13] but this effect is lower or even absent in several cancer cell lines [14]. The biological effects of this class of peptides and their ubiquitous presence in prokaryotic and eukaryotic cells indicate that they could be involved in a conserved mechanism of cell growth control and gene expression Their low concentration in cancer cells DNA as compared to normal cells indicates that this putative control mechanism may be lost during carcinogenesis. Of interest to investigate their potential role in controlling cell proliferation
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