Selective Photo-Crosslinking Detection of Methylated Cytosine in DNA Duplex Aided by a Cationic Comb-Type Copolymer

Selective Photo-Crosslinking Detection of Methylated Cytosine in DNA Duplex Aided by a Cationic Comb-Type Copolymer
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DOI:
10.1021/acsbiomaterials.2c00048
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发表时间:
2022-05-09
影响因子:
5.8
通讯作者:
Yamayoshi, Asako
Yamayoshi, Asako
中科院分区:
工程技术2区
文献类型:
--
作者:
Kojima, Atsuhiro;Nakao, Juki;Yamayoshi, Asako

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在细胞发育和分化过程中,胞嘧啶(5-甲基胞嘧啶:5-mC)基因组DNA的C-5-甲基化是一个重要的转录调节因子,在分化和未分化状态之间切换。此外,异常DNA甲基化通常存在于肿瘤抑制基因中,并且与许多疾病相关。因此,5-mC检测技术在分子生物学和癌症等疾病诊断领域是一个重要的工具。本研究发现,在阳离子梳型共聚物聚烯丙基胺-接枝葡聚糖(PAA-g-Dex)存在下,Ps-Oligo与含有5-mC的双链DNA(ds-DNA)具有新型的光交联特性,PAA-g-Dex的存在显著提高了Ps-Oligo与ds-DNA中5-mC的光交联效率,从而实现了5-mC靶向交联。我们认为PAA-g-Dex和Ps-Oligo的联合应用将成为检测基因组DNA中5-mCin的有效工具
In the process of cell development and differentiation, C-5-methylation of cytosine (5-methylcytosine: 5-mC) ingenome DNA is an important transcriptional regulator that switches between differentiated and undifferentiated states. Further,abnormal DNA methylations are often present in tumor suppressor genes and are associated with many diseases. Therefore, 5-mCdetection technology is an important tool in the most excitingfields of molecular biology and diagnosing diseases such as cancers. Inthis study, we found a novel photo-crosslinking property of psoralen-conjugated oligonucleotide (Ps-Oligo) to the double-strandedDNA (ds-DNA) containing 5-mC in the presence of a cationic comb-type copolymer, poly(allylamine)-graft-dextran (PAA-g-Dex).Photo-crosslinking efficiency of Ps-Oligo to 5-mC in ds-DNA was markedly enhanced in the presence of PAA-g-Dex, permitting 5-mC-targeted crosslinking. We believe that the combination of PAA-g-Dex and Ps-Oligo will be an effective tool for detecting 5-mCin genomic DNA