DNA 损伤反应中蛋白质组装的多尺度图谱。

IF 9 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Cell Systems Pub Date : 2023-06-21 Epub Date: 2023-05-22 DOI:10.1016/j.cels.2023.04.007
Anton Kratz, Minkyu Kim, Marcus R Kelly, Fan Zheng, Christopher A Koczor, Jianfeng Li, Keiichiro Ono, Yue Qin, Christopher Churas, Jing Chen, Rudolf T Pillich, Jisoo Park, Maya Modak, Rachel Collier, Kate Licon, Dexter Pratt, Robert W Sobol, Nevan J Krogan, Trey Ideker
{"title":"DNA 损伤反应中蛋白质组装的多尺度图谱。","authors":"Anton Kratz, Minkyu Kim, Marcus R Kelly, Fan Zheng, Christopher A Koczor, Jianfeng Li, Keiichiro Ono, Yue Qin, Christopher Churas, Jing Chen, Rudolf T Pillich, Jisoo Park, Maya Modak, Rachel Collier, Kate Licon, Dexter Pratt, Robert W Sobol, Nevan J Krogan, Trey Ideker","doi":"10.1016/j.cels.2023.04.007","DOIUrl":null,"url":null,"abstract":"<p><p>The DNA damage response (DDR) ensures error-free DNA replication and transcription and is disrupted in numerous diseases. An ongoing challenge is to determine the proteins orchestrating DDR and their organization into complexes, including constitutive interactions and those responding to genomic insult. Here, we use multi-conditional network analysis to systematically map DDR assemblies at multiple scales. Affinity purifications of 21 DDR proteins, with/without genotoxin exposure, are combined with multi-omics data to reveal a hierarchical organization of 605 proteins into 109 assemblies. The map captures canonical repair mechanisms and proposes new DDR-associated proteins extending to stress, transport, and chromatin functions. We find that protein assemblies closely align with genetic dependencies in processing specific genotoxins and that proteins in multiple assemblies typically act in multiple genotoxin responses. Follow-up by DDR functional readouts newly implicates 12 assembly members in double-strand-break repair. The DNA damage response assemblies map is available for interactive visualization and query (ccmi.org/ddram/).</p>","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":null,"pages":null},"PeriodicalIF":9.0000,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10330685/pdf/","citationCount":"0","resultStr":"{\"title\":\"A multi-scale map of protein assemblies in the DNA damage response.\",\"authors\":\"Anton Kratz, Minkyu Kim, Marcus R Kelly, Fan Zheng, Christopher A Koczor, Jianfeng Li, Keiichiro Ono, Yue Qin, Christopher Churas, Jing Chen, Rudolf T Pillich, Jisoo Park, Maya Modak, Rachel Collier, Kate Licon, Dexter Pratt, Robert W Sobol, Nevan J Krogan, Trey Ideker\",\"doi\":\"10.1016/j.cels.2023.04.007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The DNA damage response (DDR) ensures error-free DNA replication and transcription and is disrupted in numerous diseases. An ongoing challenge is to determine the proteins orchestrating DDR and their organization into complexes, including constitutive interactions and those responding to genomic insult. Here, we use multi-conditional network analysis to systematically map DDR assemblies at multiple scales. Affinity purifications of 21 DDR proteins, with/without genotoxin exposure, are combined with multi-omics data to reveal a hierarchical organization of 605 proteins into 109 assemblies. The map captures canonical repair mechanisms and proposes new DDR-associated proteins extending to stress, transport, and chromatin functions. We find that protein assemblies closely align with genetic dependencies in processing specific genotoxins and that proteins in multiple assemblies typically act in multiple genotoxin responses. Follow-up by DDR functional readouts newly implicates 12 assembly members in double-strand-break repair. The DNA damage response assemblies map is available for interactive visualization and query (ccmi.org/ddram/).</p>\",\"PeriodicalId\":54348,\"journal\":{\"name\":\"Cell Systems\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":9.0000,\"publicationDate\":\"2023-06-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10330685/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Systems\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.cels.2023.04.007\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/5/22 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Systems","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cels.2023.04.007","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/5/22 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

DNA 损伤应答(DDR)确保了无差错的 DNA 复制和转录,并在许多疾病中被破坏。目前的一项挑战是确定协调 DDR 的蛋白质及其复合物组织,包括组成性相互作用和对基因组损伤的反应。在这里,我们利用多条件网络分析系统地绘制了多种尺度的 DDR 组合图。21 种 DDR 蛋白的亲和纯化(有/无基因毒性暴露)与多组学数据相结合,揭示了 605 种蛋白组成 109 个集合体的分层组织。该图谱捕捉到了典型的修复机制,并提出了扩展到应激、转运和染色质功能的新的 DDR 相关蛋白。我们发现,蛋白质组合与处理特定基因毒素的遗传依赖性密切相关,多个组合中的蛋白质通常在多种基因毒素反应中发挥作用。通过对 DDR 功能读数的跟踪,新发现有 12 个集合体成员参与了双链断裂修复。DNA损伤应答装配图可用于交互式可视化和查询(ccmi.org/ddram/)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
A multi-scale map of protein assemblies in the DNA damage response.

The DNA damage response (DDR) ensures error-free DNA replication and transcription and is disrupted in numerous diseases. An ongoing challenge is to determine the proteins orchestrating DDR and their organization into complexes, including constitutive interactions and those responding to genomic insult. Here, we use multi-conditional network analysis to systematically map DDR assemblies at multiple scales. Affinity purifications of 21 DDR proteins, with/without genotoxin exposure, are combined with multi-omics data to reveal a hierarchical organization of 605 proteins into 109 assemblies. The map captures canonical repair mechanisms and proposes new DDR-associated proteins extending to stress, transport, and chromatin functions. We find that protein assemblies closely align with genetic dependencies in processing specific genotoxins and that proteins in multiple assemblies typically act in multiple genotoxin responses. Follow-up by DDR functional readouts newly implicates 12 assembly members in double-strand-break repair. The DNA damage response assemblies map is available for interactive visualization and query (ccmi.org/ddram/).

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Cell Systems
Cell Systems Medicine-Pathology and Forensic Medicine
CiteScore
16.50
自引率
1.10%
发文量
84
审稿时长
42 days
期刊介绍: In 2015, Cell Systems was founded as a platform within Cell Press to showcase innovative research in systems biology. Our primary goal is to investigate complex biological phenomena that cannot be simply explained by basic mathematical principles. While the physical sciences have long successfully tackled such challenges, we have discovered that our most impactful publications often employ quantitative, inference-based methodologies borrowed from the fields of physics, engineering, mathematics, and computer science. We are committed to providing a home for elegant research that addresses fundamental questions in systems biology.
期刊最新文献
pH and buffering capacity: Fundamental yet underappreciated drivers of algal-bacterial interactions What’s driving rhythmic gene expression: Sleep or the clock? Model integration of circadian- and sleep-wake-driven contributions to rhythmic gene expression reveals distinct regulatory principles On knowing a gene: A distributional hypothesis of gene function Acute response to pathogens in the early human placenta at single-cell resolution
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1