生物谷综合：据《中日新闻》报道，名古屋市立大学研究院医学研究部专家日前对外宣布，一项早期掌握基因受损程度、防止细胞癌变的研究项目取得重大成果。
因放射线或烟尘等致癌物质对DNA的损伤，会导致缺陷细胞增生。人类等生物的DNA一旦受到损伤，DNA的读取及复制功能就会中断，尽管自身带有抑制细胞增生的功能，但其具体结构尚不清楚。
细胞核内存在被DNA紧密缠绕的组蛋白，蛋白质在细胞的基因调控中起作用也是肯定的，研究人员从蛋白质与基因读取及复制有关系相关联开始着手研究，对到底是起什么作用的酶CHK1进行了调查。
研究人员用鼠做实验，发现将依附于组蛋白的CHK1人工损伤，结果显示老鼠的癌发病率很高，由此得出CHK1掌管着基因，也起到读取和开关作用。
实验表明，一旦DNA受损，CHK1就与组蛋白分离，构成组蛋白的部分氨基酸发生化学变化，其开关呈关闭状，不起复制作用。一旦因遗传或致癌物质的影响，酶的功能消失，开关不仅不关闭，还会增生带有损伤信息的缺陷细胞。
研究小组的中西真教授和岛田绿研究员表示，沿着这个思路研究下去，开发恢复酶功能的药物，癌的预防是可行的。
该研究成果论文登载在美国科技期刊《细胞》上。（生物谷援引科技部）
生物谷推荐原始出处：
Cell, Vol 132, 221-232, 25 January 2008
Article
Chk1 Is a Histone H3 Threonine 11 Kinase that Regulates DNA Damage-Induced Transcriptional Repression
Midori Shimada,1 Hiroyuki Niida,1 Doaa H. Zineldeen,1 Hideaki Tagami,2 Masafumi Tanaka,3 Hiroyuki Saito,3 and Makoto Nakanishi1,
1 Department of Cell Biology and Biochemistry, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan
2 Graduate School of Natural Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan
3 Laboratory of Biophysical Chemistry, Kobe Pharmaceutical University, Motoyama Kita-machi, Higashinada-ku, Kobe 658-8558, Japan
Corresponding author
Makoto Nakanishi
mkt-naka@med.nagoya-cu.ac.jp
DNA damage results in activation or suppression of transcription of a large number of genes. Transcriptional activation has been well characterized in the context of sequence-specific DNA-bound activators, whereas mechanisms of transcriptional suppression are largely unexplored. We show here that DNA damage rapidly reduces histone H3 Threonine 11 (T11) phosphorylation. This correlates with repression of genes, including cyclin B1 and cdk1. H3-T11 phosphorylation occurs throughout the cell cycle and is Chk1 dependent in vivo. Following DNA damage, Chk1 undergoes rapid chromatin dissociation, concomitant with reduced H3-T11 phosphorylation. Furthermore, we find that loss of H3-T11 phosphorylation correlates with reduced binding of the histone acetyltransferase GCN5 at cyclin B1 and cdk1 promoters and reduced H3-K9 acetylation. We propose a mechanism for Chk1 as a histone kinase, responsible for DNA-damage-induced transcriptional repression by loss of histone acetylation.
