5-Hydroxymethylcytosine is a predominantly stable DNA modification.
5-Hydroxymethylcytosine is a predominantly stable DNA modification.
复制标题
作者：
5-羟甲基胞嘧啶（hmC）是存在于大多数哺乳动物细胞DNA中的5-甲基胞嘧啶（mC）的氧化产物。DNA中hmC水平的降低是癌症的标志。阐明这种氧化反应的动力学和hmC在DNA中的寿命是理解hmC功能的基础。使用稳定的同位素标记的哺乳动物细胞的DNA中的胞嘧啶衍生物和超灵敏的串联液相色谱质谱（LCMS），我们表明，大多数hmC是一个稳定的修改，而不是一个短暂的中间体。与DNA甲基化（在复制过程中立即发生）相反，hmC在DNA合成后的前30小时内缓慢形成。小鼠组织中DNA的同位素标记证实了hmC在体内的稳定性，并证明了hmC的总体水平与细胞增殖之间的关系。这些见解对于理解健康和疾病中化学修饰的DNA碱基的状态具有重要意义。
5-Hydroxymethylcytosine (hmC) is an oxidation product of 5-methylcytosine (mC) present in DNA of most mammalian cells. Reduction of hmC levels in DNA is a hallmark of cancers. Elucidating the dynamics of this oxidation reaction and the lifetime of hmC in DNA is fundamental to understanding hmC function. Using stable isotope labeling of cytosine derivatives in the DNA of mammalian cells and ultrasensitive tandem liquid-chromatography mass spectrometry (LCMS), we show that the majority of hmC is a stable modification, as opposed to a transient intermediate. In contrast with DNA methylation, which occurs immediately during replication, hmC forms slowly over the first 30 h following DNA synthesis. Isotopic labeling of DNA in mouse tissues confirmed the stability of hmC in vivo and demonstrated a relationship between global levels of hmC and cell proliferation. These insights have important implications for understanding the states of chemically modified DNA bases in health and disease.
登录
查看更多内容
影响因子：
23.9
作者：
Dawlaty, Meelad M.;Ganz, Kibibi;Powell, Benjamin E.;Hu, Yueh-Chiang;Markoulaki, Styliani;Cheng, Albert W.;Gao, Qing;Kim, Jongpil;Choi, Sang-Woon;Page, David C.;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
影响因子：
13.8
作者：
Song, Chun-Xiao;He, Chuan
通讯作者：
He, Chuan
影响因子：
3.7
作者：
Globisch D;Münzel M;Müller M;Michalakis S;Wagner M;Koch S;Brückl T;Biel M;Carell T
通讯作者：
Carell T
影响因子：
6.4
作者：
Kraus, Theo F. J.;Globisch, Daniel;Kretzschmar, Hans A.
通讯作者：
Kretzschmar, Hans A.
影响因子：
3.7
作者：
Otani J;Kimura H;Sharif J;Endo TA;Mishima Y;Kawakami T;Koseki H;Shirakawa M;Suetake I;Tajima S
通讯作者：
Tajima S