UV damage induces production of mitochondrial DNA fragments with specific length profiles.
UV damage induces production of mitochondrial DNA fragments with specific length profiles.
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紫外线损伤会诱导产生具有特定长度特征的线粒体 DNA 片段。
DOI：
10.1101/2023.11.07.566130
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Sloan,DanielB
中科院分区：
文献类型：
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作者：
Waneka,Gus;Stewart,Joseph;Anderson,JohnR;Li,Wentao;Wilusz,Jeffrey;Argueso,JuanLucas;Sloan,DanielB
紫外线是一种强诱变剂，可诱导环丁烷嘧啶二聚体（CPD）形式的大体积DNA损伤。核基因组中发生的光损伤和其他大块病变可以通过核苷酸切除修复（NER）进行修复，其中受损部位两侧的切口先于含有损伤的单链寡核苷酸的去除。线粒体基因组（mtDNA）也容易受到紫外线的损伤，但目前的证据表明，消除庞大的mtDNA损伤的唯一方法是通过mtDNA降解。在NER期间切除的含有损伤的寡核苷酸可以用抗损伤抗体捕获并测序（XR-seq），以产生UV暴露后活性修复位置的高分辨率地图。我们分析了先前发表的来自拟南芥、酿酒酵母和黑腹果蝇的数据集，以识别来自线粒体DNA（和A. thaliana）。在A。thalianaandS.在酿酒酵母中，与核作图读数相比，mtDNA作图读数具有独特的长度分布。优势片段大小为26 nt，A为28 nt。有明显的第二个高峰出现在规则的时间间隔。这些读数还显示二嘧啶（CPD形成的底物）的非随机分布，其中TT富集在读数的位置7-8处。因此，紫外线对线粒体DNA的损伤似乎导致产生特征长度和相对于损伤位置的位置的DNA片段。产生这些片段的机制尚不清楚，但我们假设它们是由线粒体中以前未表征的DNA降解途径或修复机制引起的。
UV light is a potent mutagen that induces bulky DNA damage in the form of cyclobutane pyrimidine dimers (CPDs). Photodamage and other bulky lesions occurring in nuclear genomes can be repaired through nucleotide excision repair (NER), where incisions on both sides of a damaged site precede the removal of a single-stranded oligonucleotide containing the damage. Mitochondrial genomes (mtDNAs) are also susceptible to damage from UV light, but current evidence suggests that the only way to eliminate bulky mtDNA damage is through mtDNA degradation. Damage-containing oligonucleotides excised during NER can be captured with antidamage antibodies and sequenced (XR-seq) to produce high-resolution maps of active repair locations following UV exposure. We analyzed previously published datasets fromArabidopsis thaliana, Saccharomyces cerevisiae, andDrosophila melanogasterto identify reads originating from the mtDNA (and plastid genome inA. thaliana). InA. thalianaandS. cerevisiae, the mtDNA-mapping reads have unique length distributions compared to the nuclear-mapping reads. The dominant fragment size was 26 nt inS. cerevisiaeand 28 nt inA. thalianawith distinct secondary peaks occurring in regular intervals. These reads also show a nonrandom distribution of di-pyrimidines (the substrate for CPD formation) with TT enrichment at positions 7–8 of the reads. Therefore, UV damage to mtDNA appears to result in production of DNA fragments of characteristic lengths and positions relative to the damaged location. The mechanisms producing these fragments are unclear, but we hypothesize that they result from a previously uncharacterized DNA degradation pathway or repair mechanism in mitochondria.