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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Homologous chromosomes make contact at the sites of double-strand breaks in genes in somatic G_0/G_rphase human cells
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Homologous chromosomes make contact at the sites of double-strand breaks in genes in somatic G_0/G_rphase human cells

机译：同源染色体在体细胞G_0 / G_rphase人类细胞中的基因双链断裂位点接触

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摘要

Double-strand DNA breaks (DSBs) are continuously induced in cells by endogenously generated free radicals and exogenous geno-toxic agents such as ionizing radiation. DSBs activate the kinase activity in sensor proteins such as ATM and DNA-PK, initiating a complex DNA damage response that coordinates various DNA repair pathways to restore genomic integrity. In this study, we report the unexpected finding that homologous chromosomes contact each other at the sites of DSBs induced by either radiation or the endonuclease I-Ppol in human somatic cells. Contact involves short segments of homologous chromosomes and is centered on a DSB in active genes but does not occur at I-Ppol sites in intergenic DNA. l-Ppol-induced contact between homologous genes is abrogated by the transcriptional inhibitors actinomycin D and a-amanitin and requires the kinase activity of ATM but not DNA-PK. Our findings provide documentation of a common transcription-related and ATM kinase-dependent mechanism that induces contact between allelic regions of homologous chromosomes at sites of DSBs in human somatic cells.
机译：双链DNA断裂（DSB）由内源性产生的自由基和外源性遗传毒性剂（例如电离辐射）连续诱导在细胞中。 DSB激活传感器蛋白（如ATM和DNA-PK）中的激酶活性，引发复杂的DNA损伤反应，协调各种DNA修复途径以恢复基因组完整性。在这项研究中，我们报告了一个出乎意料的发现，即在人类体细胞中，同源染色体在由辐射或核酸内切酶I-Ppol诱导的DSBs部位彼此接触。接触涉及同源染色体的短片段，并以活跃基因中的DSB为中心，但不在基因间DNA的I-Ppol位点发生。转录抑制剂放线菌素D和α-amanitin消除了l-Ppol诱导的同源基因之间的接触，并需要ATM的激酶活性，但不需要DNA-PK。我们的发现提供了一种常见的转录相关和ATM激酶依赖性机制的文献，该机制可诱导人体细胞中DSB位置的同源染色体等位基因区域之间的接触。

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  • 作者

    Manoj Gandhi; Viktoria N.Evdokimova; Karen T.Cuenco; Marina N.Nikiforova; Lindsey M.Kelly; James R.Stringer; Christopher J.Bakkenist; Yuri E.Nikiforov;

  • 作者单位

    Department of Pathology and Laboratory Medicine, University of Pittsburgh, Pittsburgh, PA 15213;

    Department of Pathology and Laboratory Medicine, University of Pittsburgh, Pittsburgh, PA 15213;

    Department of Oral Biology, School of Dental Medicine and University of Pittsburgh, Pittsburgh, PA 15219,Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15219;

    Department of Pathology and Laboratory Medicine, University of Pittsburgh, Pittsburgh, PA 15213;

    Department of Pathology and Laboratory Medicine, University of Pittsburgh, Pittsburgh, PA 15213;

    Department of Molecular Genetics,University of Cincinnati, Cincinnati, OH 45267;

    Department of Molecular Genetics,University of Cincinnati, Cincinnati, OH 45267,Departments of Radiation Oncology and Pharmacology and Chemical Biology, University of Pittsburgh,Pittsburgh, PA 15213;

    Department of Pathology and Laboratory Medicine, University of Pittsburgh, Pittsburgh, PA 15213;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    homologous chromosome interaction; homologous recombination;

    机译：同源染色体相互作用同源重组;

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