摘要
我们的前期研究在乳腺癌细胞SKBR3中首次检测到了组蛋白H2A.X第39位酪氨酸残基(Y39)可以发生磷酸化修饰(H2A.X^(Y39ph))。该位点的磷酸化修饰是γ-H2A.X正确形成的必要条件,并促进损伤修复因子募集到DNA损伤区域,有助于损伤修复反应。经过深入研究,我们又发现磷酸酶分子EYA2(eyes absent 2)能够去除乳腺癌细胞SKBR3中H2A.X^(Y39)位点的磷酸化修饰。在DNA损伤后,与H2A.X结合的EYA2蛋白减少,这可能是DNA损伤修复阶段H2A.X^(Y39ph)水平上调的原因。乳腺癌细胞中低水平的EYA2通过上调H2A.X^(Y39ph)水平及下游增殖相关基因转录促进细胞增殖。我们的报道为H2A.X^(Y39ph)功能的深入研究提供了数据基础。
In our previous study, we firstly found that the 39th tyrosine residue (Y39) ofhistone H2A.X could be phosphorylated to form H2A.X^Y39 in breast cancer cell SKBR3. The phosphorylation modification of this site-Y39 was a necessary condition for the correct formation of γ-H2A, and it could promote the recruitment of damage repair factors to DNA damage region, which was helpful to the damage repair response. After in-depth study, we also discovered that the phosphatase molecule EYA2 (eyes absent 2) could dephosphorylate H2A.X^Y39 in breast cancer cell SKBR3. After DNA damage, EYA2 binding to H2A.X was decreased, which might be the reason for the increase of H2A.X^T39ph during DNA damage repair stage. Low level of EYA2 could promote cell proliferation by up-regulating the level of H2A.X^Y39ph and the transcription level of downstream proliferation related gene in breast cancer cells. Our study provided a data base for the further research ofH2A.X^T39ph function.
出处
《基因组学与应用生物学》
CAS
CSCD
北大核心
2017年第3期1167-1172,共6页
Genomics and Applied Biology
基金
国家自然科学基金(81302324)资助