Uhrf2 is important for DNA damage response in vascular smooth muscle cells

被引:19
作者
Luo, Tao [1 ]
Cui, Shijun [1 ]
Bian, Chunjing [2 ]
Yu, Xiaochun [2 ]
机构
[1] Capital Med Univ, Dept Vasc Surg, Xuan Wu Hosp, Inst Vasc Surg, Beijing, Peoples R China
[2] Univ Michigan, Sch Med, Dept Internal Med, Div Mol Med & Genet, Ann Arbor, MI 48109 USA
关键词
Uhrf2; DNA damage response; DNA damage repair; HEMI-METHYLATED DNA; EPIGENETIC INHERITANCE; GENOMIC INSTABILITY; MULTIDOMAIN PROTEIN; HISTONE H2AX; SRA DOMAIN; STEM-CELLS; RECOGNITION; BINDING; GENE;
D O I
10.1016/j.bbrc.2013.10.018
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Emerging evidence shows that Uhrf1 plays an important role in DNA damage response for maintaining genomic stability. Interestingly, Uhrf1 has a paralog Uhrf2 in mammals. Uhrf1 and Uhrf2 share similar domain architectures. However, the role of Uhrf2 in DNA damage response has not been studied yet. During the analysis of the expression level of Uhrf2 in different tissues, we found that Uhrf2 is highly expressed in aorta and aortic vascular smooth muscle cells. Thus, we studied the role of Uhrf2 in DNA damage response in aortic vascular smooth muscle cells. Using laser microirradiation, we found that like Uhrf1, Uhrf2 was recruited to the sites of DNA damage. We dissected the functional domains of Uhrf2 and found that the TTD, PHD and SRA domains are important for the relocation of Uhrf2 to the sites of DNA damage. Moreover, depletion of Uhrf2 suppressed DNA damage-induced H2AX phosphorylation and DNA damage repair. Taken together, our results demonstrate the function of Uhrf2 in DNA damage response. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:65 / 70
页数:6
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