Han-Wen Chang, Ekaterina V Nizovtseva, Sergey V Razin, Tim Formosa, Katerina V Gurova, Vasily M Studitsky
{"title":"组蛋白伴侣 FACT 和 Curaxins:对基因组结构和功能的影响","authors":"Han-Wen Chang, Ekaterina V Nizovtseva, Sergey V Razin, Tim Formosa, Katerina V Gurova, Vasily M Studitsky","doi":"10.20517/2394-4722.2019.31","DOIUrl":null,"url":null,"abstract":"<p><p>The histone chaperone FACT plays important roles in essentially every chromatin-associated process and is an important indirect target of the curaxin class of anti-cancer drugs. Curaxins are aromatiс compounds that intercalate into DNA and can trap FACT in bulk chromatin, thus interfering with its distribution and its functions in cancer cells. Recent studies have provided mechanistic insight into how FACT and curaxins cooperate to promote unfolding of nucleosomes and chromatin fibers, resulting in genome-wide disruption of contact chromatin domain boundaries, perturbation of higher order chromatin organization, and global disregulation of gene expression. Here, we discuss the implications of these insights for cancer biology.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"5 ","pages":""},"PeriodicalIF":1.4000,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6919649/pdf/nihms-1062752.pdf","citationCount":"0","resultStr":"{\"title\":\"Histone Chaperone FACT and Curaxins: Effects on Genome Structure and Function.\",\"authors\":\"Han-Wen Chang, Ekaterina V Nizovtseva, Sergey V Razin, Tim Formosa, Katerina V Gurova, Vasily M Studitsky\",\"doi\":\"10.20517/2394-4722.2019.31\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The histone chaperone FACT plays important roles in essentially every chromatin-associated process and is an important indirect target of the curaxin class of anti-cancer drugs. Curaxins are aromatiс compounds that intercalate into DNA and can trap FACT in bulk chromatin, thus interfering with its distribution and its functions in cancer cells. Recent studies have provided mechanistic insight into how FACT and curaxins cooperate to promote unfolding of nucleosomes and chromatin fibers, resulting in genome-wide disruption of contact chromatin domain boundaries, perturbation of higher order chromatin organization, and global disregulation of gene expression. Here, we discuss the implications of these insights for cancer biology.</p>\",\"PeriodicalId\":15167,\"journal\":{\"name\":\"Journal of Cancer Metastasis and Treatment\",\"volume\":\"5 \",\"pages\":\"\"},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2019-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6919649/pdf/nihms-1062752.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Cancer Metastasis and Treatment\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.20517/2394-4722.2019.31\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2019/11/29 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cancer Metastasis and Treatment","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.20517/2394-4722.2019.31","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2019/11/29 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
组蛋白伴侣 FACT 在几乎所有染色质相关过程中都发挥着重要作用,也是箭毒素类抗癌药物的一个重要间接靶点。茄红素是一种芳香族化合物,可插入 DNA 并将 FACT 困在大量染色质中,从而干扰其在癌细胞中的分布和功能。最近的研究从机理上揭示了 FACT 和纤连蛋白如何合作促进核小体和染色质纤维的折叠,从而导致全基因组接触染色质结构域边界的破坏、高阶染色质组织的扰乱以及基因表达的全面失调。在此,我们将讨论这些见解对癌症生物学的影响。
Histone Chaperone FACT and Curaxins: Effects on Genome Structure and Function.
The histone chaperone FACT plays important roles in essentially every chromatin-associated process and is an important indirect target of the curaxin class of anti-cancer drugs. Curaxins are aromatiс compounds that intercalate into DNA and can trap FACT in bulk chromatin, thus interfering with its distribution and its functions in cancer cells. Recent studies have provided mechanistic insight into how FACT and curaxins cooperate to promote unfolding of nucleosomes and chromatin fibers, resulting in genome-wide disruption of contact chromatin domain boundaries, perturbation of higher order chromatin organization, and global disregulation of gene expression. Here, we discuss the implications of these insights for cancer biology.