生物谷綜合：據(jù)《中日新聞》報(bào)道，名古屋市立大學(xué)研究院醫(yī)學(xué)研究部專家日前對(duì)外宣布,，一項(xiàng)早期掌握基因受損程度,、防止細(xì)胞癌變的研究項(xiàng)目取得重大成果。
因放射線或煙塵等致癌物質(zhì)對(duì)DNA的損傷,，會(huì)導(dǎo)致缺陷細(xì)胞增生,。人類等生物的DNA一旦受到損傷，DNA的讀取及復(fù)制功能就會(huì)中斷,，盡管自身帶有抑制細(xì)胞增生的功能,，但其具體結(jié)構(gòu)尚不清楚。
細(xì)胞核內(nèi)存在被DNA緊密纏繞的組蛋白,，蛋白質(zhì)在細(xì)胞的基因調(diào)控中起作用也是肯定的,，研究人員從蛋白質(zhì)與基因讀取及復(fù)制有關(guān)系相關(guān)聯(lián)開始著手研究，對(duì)到底是起什么作用的酶CHK1進(jìn)行了調(diào)查,。
研究人員用鼠做實(shí)驗(yàn),，發(fā)現(xiàn)將依附于組蛋白的CHK1人工損傷,，結(jié)果顯示老鼠的癌發(fā)病率很高，由此得出CHK1掌管著基因,，也起到讀取和開關(guān)作用,。
實(shí)驗(yàn)表明，一旦DNA受損,，CHK1就與組蛋白分離,，構(gòu)成組蛋白的部分氨基酸發(fā)生化學(xué)變化，其開關(guān)呈關(guān)閉狀,，不起復(fù)制作用,。一旦因遺傳或致癌物質(zhì)的影響，酶的功能消失,，開關(guān)不僅不關(guān)閉,，還會(huì)增生帶有損傷信息的缺陷細(xì)胞。
研究小組的中西真教授和島田綠研究員表示,，沿著這個(gè)思路研究下去,，開發(fā)恢復(fù)酶功能的藥物，癌的預(yù)防是可行的,。
該研究成果論文登載在美國(guó)科技期刊《細(xì)胞》上,。（生物谷援引科技部）
生物谷推薦原始出處：
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
[email protected]
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.
