组蛋白H2A.X酪氨酸142位点磷酸化：细胞凋亡的一种新型开关？

Histone H2A.X Tyr142 phosphorylation: a novel sWItCH for apoptosis?

作者信息

Stucki Manuel

机构信息

Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.

出版信息

DNA Repair (Amst). 2009 Jul 4;8(7):873-6. doi: 10.1016/j.dnarep.2009.04.003. Epub 2009 May 14.

DOI:10.1016/j.dnarep.2009.04.003

PMID:19446503

Abstract

Histone H2A.X phosphorylation on Ser139 in response to DNA damage is the major signal for the assembly of the so-called gammaH2A.X chromatin domain, a region surrounding an unrepaired DNA double-strand break that is characterized by the accumulation of a large number of DNA damage response proteins. However, it is not yet clear how this event is regulated in space and time. The recent discovery of H2A.X Tyr142 phosphorylation by the WICH complex and its dephosphorylation by the EYA1/3 phosphatases may provide substantial novel insight into this process. WSTF, a subunit of the WICH complex bears a novel kinase domain at its N-terminus that constitutively targets H2A.X on Tyr142. This novel histone modification appears to determine the relative recruitment of either DNA repair or pro-apoptotic factors to sites of DNA damage. Thus, the balance of H2A.X Tyr142 phosphorylation/dephosphorylation may constitute a novel switch mechanism to determine cell fate after DNA damage.

摘要

响应DNA损伤时，组蛋白H2A.X在丝氨酸139位点的磷酸化是所谓γH2A.X染色质结构域组装的主要信号，该结构域围绕未修复的DNA双链断裂区域，其特征是大量DNA损伤反应蛋白的积累。然而，目前尚不清楚这一事件在时空上是如何被调控的。最近发现WICH复合物可使H2A.X在酪氨酸142位点磷酸化，而EYA1/3磷酸酶可使其去磷酸化，这可能为该过程提供重要的新见解。WSTF是WICH复合物的一个亚基，在其N端带有一个新的激酶结构域，该结构域持续靶向H2A.X的酪氨酸142位点。这种新的组蛋白修饰似乎决定了DNA修复或促凋亡因子向DNA损伤位点的相对募集。因此，H2A.X酪氨酸142位点磷酸化/去磷酸化的平衡可能构成一种新的开关机制，以决定DNA损伤后细胞的命运。