真核細(xì)胞修復(fù)DNA雙鏈斷裂很重要,，因為如果做不到這一點(diǎn),，會引起基因組不穩(wěn)定,、癌變和細(xì)胞死亡,。細(xì)胞對哺乳動物體內(nèi)DNA雙鏈斷裂的一個早期響應(yīng)是,，專用組蛋白H2A.X（被稱為“兔抗”）在“絲氨酸139”處所發(fā)生的磷酸化,。H2A.X是組蛋白的衍生物，H2A.X磷酸化也是細(xì)胞凋亡標(biāo)志之一,。

現(xiàn)在,，研究人員又發(fā)現(xiàn)了一個以前人們所不知道的H2A.X磷酸化點(diǎn)，其位置在“酪氨酸142”處,。在這個位置所發(fā)生的磷酸化由染色質(zhì)重塑因子WSTF催化,，該因子在Williams–Beuren綜合癥（一種由人類7號染色體刪除所引起的一種發(fā)育疾病）患者身上經(jīng)常缺失,。這項工作引起人們對在哺乳動物細(xì)胞DNA損傷響應(yīng)過程中專門調(diào)控染色質(zhì)重組的一個新穎通道的注意,，并且為了解Williams–Beuren綜合癥的分子基礎(chǔ)提供了線索,。（生物谷Bioon.com）

生物谷推薦原始出處：

Nature 457, 57-62 (1 January 2009) | doi:10.1038/nature07668

WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity

Andrew Xiao1, Haitao Li2, David Shechter1, Sung Hee Ahn1, Laura A. Fabrizio3, Hediye Erdjument-Bromage3, Satoko Ishibe-Murakami2, Bin Wang4, Paul Tempst3, Kay Hofmann5, Dinshaw J. Patel2, Stephen J. Elledge4 & C. David Allis1

1 Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10065, USA
2 Structural Biology Program,
3 Molecular Biology Program, Memorial-Sloan-Kettering Cancer Center, New York, New York 10065, USA
4 Howard Hughes Medical Institute, Department of Genetics, Harvard Partners Center for Genetics and Genomics, Harvard Medical School, Boston, Massachusetts 02115, USA
5 Miltenyi Biotec GmbH, 50829 Koeln, Germany

DNA double-stranded breaks present a serious challenge for eukaryotic cells. The inability to repair breaks leads to genomic instability, carcinogenesis and cell death. During the double-strand break response, mammalian chromatin undergoes reorganization demarcated by H2A.X Ser 139 phosphorylation (-H2A.X). However, the regulation of -H2A.X phosphorylation and its precise role in chromatin remodelling during the repair process remain unclear. Here we report a new regulatory mechanism mediated by WSTF (Williams–Beuren syndrome transcription factor, also known as BAZ1B)—a component of the WICH complex (WSTF–ISWI ATP-dependent chromatin-remodelling complex). We show that WSTF has intrinsic tyrosine kinase activity by means of a domain that shares no sequence homology to any known kinase fold. We show that WSTF phosphorylates Tyr 142 of H2A.X, and that WSTF activity has an important role in regulating several events that are critical for the DNA damage response. Our work demonstrates a new mechanism that regulates the DNA damage response and expands our knowledge of domains that contain intrinsic tyrosine kinase activity.