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Abstract <p>When DNA repair is completed, the processes associated with the restoration of the normal chromatin structure play an important role. Incorrect chromatin assembly can lead to genomic rearrangements, which, in turn, can cause the development of many diseases, including cancer. Previously, we showed that violations of the correct assembly of nucleosomes and their remodulation during the reparative assembly of chromatin lead to an increased level of mutagenesis. In this work, we have shown that the <i>asf1</i>Δ mutation has a constitutively hyperactivated Rad53 kinase, which causes disorganization of the chromatin structure and significantly changes the spectrum of spontaneous reparative mutations. Violation of the binding site of the Rad9 adaptive protein to DNA as a result of inactivation of the <i>DOT1</i> gene eliminates <i>hif1</i>Δ<i>-</i>specific mutagenesis, which is a consequence of incorrect reparative assembly of nucleosomes. The absence of the Rad9 protein under normal growth conditions and when treated with low doses of UV rays leads to aberrant activation of the RNR complex. At the same time, a further increase in the dose of UV radiation practically does not affect the expression of <i>RNR3</i>. These results confirm that correct chromatin assembly is critical for the normal functioning of the genome.</p>

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Reparative Chromatin Assembly Plays an Important Role in Genome Stability

  • 期刊论文

  • 发表日期：

    2025年2月1日

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  • I. I. Skobeleva,
  • T. A. Evstyukhina,
  • E. A. Alekseeva,
  • A. V. Toroshchina,
  • V. T. Peshekhonov,
  • D. V. Fedorov,
  • V. G. Korolev

摘要

Abstract

When DNA repair is completed, the processes associated with the restoration of the normal chromatin structure play an important role. Incorrect chromatin assembly can lead to genomic rearrangements, which, in turn, can cause the development of many diseases, including cancer. Previously, we showed that violations of the correct assembly of nucleosomes and their remodulation during the reparative assembly of chromatin lead to an increased level of mutagenesis. In this work, we have shown that the asf1Δ mutation has a constitutively hyperactivated Rad53 kinase, which causes disorganization of the chromatin structure and significantly changes the spectrum of spontaneous reparative mutations. Violation of the binding site of the Rad9 adaptive protein to DNA as a result of inactivation of the DOT1 gene eliminates hif1Δ-specific mutagenesis, which is a consequence of incorrect reparative assembly of nucleosomes. The absence of the Rad9 protein under normal growth conditions and when treated with low doses of UV rays leads to aberrant activation of the RNR complex. At the same time, a further increase in the dose of UV radiation practically does not affect the expression of RNR3. These results confirm that correct chromatin assembly is critical for the normal functioning of the genome.