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首页> 外文期刊>Nucleic Acids Research >ATP insertion opposite 8-oxo-deoxyguanosine by Pol4 mediates error-free tolerance in Schizosaccharomyces pombe
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ATP insertion opposite 8-oxo-deoxyguanosine by Pol4 mediates error-free tolerance in Schizosaccharomyces pombe

机译：通过POL4对面的8-氧代脱氧胍苷对面的ATP插入介导Schizosaccharomyces Pombe中的无差别耐受性

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摘要

7,8-Dihydro-8-oxo-deoxyguanosine (8oxodG) is a highly premutagenic DNA lesion due to its ability to mispair with adenine. Schizosaccharomyces pombe lacks homologs for relevant enzymes that repair 8oxodG, which suggests that this lesion could be persistent and must be tolerated. Here we show that SpPol4, the unique PolX in fission yeast, incorporates ATP opposite 8oxodG almost exclusively when all nucleotides (ribos and deoxys) are provided at physiological concentrations. Remarkably, this SpPol4-specific reaction could also occur during the NHEJ of DSBs. In cell extracts, misincorporation of ATP opposite 8oxodG was shown to be SpPol4-specific, although RNase H2 efficiently recognized the 8oxodG: AMP mispair to remove AMP and trigger error-free incorporation of dCTP. These data are the first evidence that ribonucleotides can be used safely for 8oxodG tolerance, suggesting that insertion of the highly abundant ATP substrate could be beneficial to promote efficient and error-free repair of 8oxodG-associated DSBs. Moreover, we demonstrate that purified SpPol4 uses 8oxo-dGTP and 8oxo-GTP as substrates for DNA polymerization, although with poor efficiency compared to the incorporation of undamaged nucleotides opposite either 8oxodG or undamaged templates. This suggests that SpPol4 is specialized in tolerating 8oxodG as a DNA template, without contributing significantly to the accumulation of this lesion in the DNA.
机译：7,8-二氢-8-氧脱氧胍（8oxodg）是一种高度高兴的DNA病变，因为它具有腺嘌呤的错配。 Schizosaccharomyces Pombe缺乏用于修复8oxodg的相关酶的同源物，这表明这种病变可能是持久的并且必须耐受。在这里，我们表明SPPOL4是裂变酵母中的独特POLX，几乎仅在生理浓度下提供所有核苷酸（核苷和脱氧）时与8oxodg相反的ATP。值得注意的是，在DSB的NHEJ期间也可能发生这种SPPOL4特异性反应。在细胞提取物中，ATP对相对的8oxodg的MISlincoration被证明是SPPOL4特异性的，尽管RNase H2有效地认识到8oxodg：AMP错误分布，以去除AMP并触发无误掺入DCTP。这些数据是第一种证据，即核糖核苷酸可以安全地用于8oxodg耐受性，表明高度丰富的ATP衬底的插入可能是有益的，促进8- oxodg相关的DSB的有效和无差无差无差无差无差无瓦修复。此外，我们证明纯化的SPPOL4使用80- oxO-DGTP和8oxO-GTP作为用于DNA聚合的底物，但与效率相比差，而未掺入未损坏的核苷酸与8oxodg或未遭受的模板相对。这表明SPPOL4专门用于将8oxodg作为DNA模板耐受，而不会显着促进DNA中该病变的积累。

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  • 来源
    《Nucleic Acids Research》 |2014年第15期|共17页
  • 作者

    Sastre-Moreno Guillermo; Sanchez Arancha; Esteban Veronica; Blanco Luis;

  • 作者单位

    Univ Autonoma Madrid Ctr Biol Mol Severo Ochoa CSIC UAM E-28049 Madrid Spain;

    Univ Autonoma Madrid Ctr Biol Mol Severo Ochoa CSIC UAM E-28049 Madrid Spain;

    Univ Autonoma Madrid Ctr Biol Mol Severo Ochoa CSIC UAM E-28049 Madrid Spain;

    Univ Autonoma Madrid Ctr Biol Mol Severo Ochoa CSIC UAM E-28049 Madrid Spain;

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  • 正文语种 eng
  • 中图分类 生物化学;
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