真核细胞修复DNA双链断裂很重要，因为如果做不到这一点，会引起基因组不稳定、癌变和细胞死亡。细胞对哺乳动物体内DNA双链断裂的一个早期响应是，专用组蛋白H2A.X（被称为“兔抗”）在“丝氨酸139”处所发生的磷酸化。H2A.X是组蛋白的衍生物，H2A.X磷酸化也是细胞凋亡标志之一。
现在，研究人员又发现了一个以前人们所不知道的H2A.X磷酸化点，其位置在“酪氨酸142”处。在这个位置所发生的磷酸化由染色质重塑因子WSTF催化，该因子在Williams–Beuren综合症（一种由人类7号染色体删除所引起的一种发育疾病）患者身上经常缺失。这项工作引起人们对在哺乳动物细胞DNA损伤响应过程中专门调控染色质重组的一个新颖通道的注意，并且为了解Williams–Beuren综合症的分子基础提供了线索。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
