UV damage induces production of mitochondrial DNA fragments with specific length profiles.

IF 3.3 3区 生物学 Q2 GENETICS & HEREDITY
Genetics Pub Date : 2024-07-08 DOI:10.1093/genetics/iyae070
Gus Waneka, Joseph Stewart, John R Anderson, Wentao Li, Jeffrey Wilusz, Juan Lucas Argueso, Daniel B Sloan
{"title":"UV damage induces production of mitochondrial DNA fragments with specific length profiles.","authors":"Gus Waneka, Joseph Stewart, John R Anderson, Wentao Li, Jeffrey Wilusz, Juan Lucas Argueso, Daniel B Sloan","doi":"10.1093/genetics/iyae070","DOIUrl":null,"url":null,"abstract":"<p><p>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 from Arabidopsis thaliana, Saccharomyces cerevisiae, and Drosophila melanogaster to identify reads originating from the mtDNA (and plastid genome in A. thaliana). In A. thaliana and S. cerevisiae, the mtDNA-mapping reads have unique length distributions compared to the nuclear-mapping reads. The dominant fragment size was 26 nt in S. cerevisiae and 28 nt in A. thaliana with 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.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228841/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/genetics/iyae070","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

Abstract

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 from Arabidopsis thaliana, Saccharomyces cerevisiae, and Drosophila melanogaster to identify reads originating from the mtDNA (and plastid genome in A. thaliana). In A. thaliana and S. cerevisiae, the mtDNA-mapping reads have unique length distributions compared to the nuclear-mapping reads. The dominant fragment size was 26 nt in S. cerevisiae and 28 nt in A. thaliana with 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.

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。
紫外线是一种强效诱变剂,能诱导环丁烷嘧啶二聚体(CPD)形式的大块 DNA 损伤。核基因组中出现的光损伤和其他大块病变可通过核苷酸切除修复(NER)进行修复,在切除含有损伤的单链寡核苷酸之前,先在损伤位点两侧切开。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,消除大块 mtDNA 损伤的唯一方法是通过 mtDNA 降解。在NER过程中切除的含损伤的寡核苷酸可以用抗损伤抗体捕获并测序(XR-seq),以产生紫外线照射后活性修复位置的高分辨率图谱。我们分析了之前发表的拟南芥、酿酒酵母和黑腹果蝇的数据集,以确定源自mtDNA(拟南芥为质体基因组)的读数。与核映射读数相比,在大连农杆菌和酿酒酵母中,mtDNA映射读数具有独特的长度分布。在 S. cerevisiae 和 A. thaliana 中,主要的片段大小分别为 26 nt 和 28 nt,并以一定的间隔出现明显的次高峰。这些读数还显示出二嘧啶(CPD 形成的底物)的非随机分布,读数的 7-8 位富含 TT。因此,紫外线对 mtDNA 的损伤似乎会导致产生相对于损伤位置的特征长度和位置的 DNA 片段。产生这些片段的机制尚不清楚,但我们推测它们是线粒体中以前未定性的 DNA 降解途径或修复机制的结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Genetics
Genetics GENETICS & HEREDITY-
CiteScore
6.90
自引率
6.10%
发文量
177
审稿时长
1.5 months
期刊介绍: GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信