Protection of internal (TTAGGG)n repeats in Chinese hamster cells by telomeric protein TRF1.

Protection of internal (TTAGGG)n repeats in Chinese hamster cells by telomeric protein TRF1.
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端粒蛋白 TRF1 对中国仓鼠细胞内部 (TTAGGG)n 重复序列的保护。

DOI:
10.1038/sj.onc.1206745
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发表时间:
2003
期刊:
Oncogene.
影响因子:
--
通讯作者:
Tomilin,NikolaiViktorovich
Tomilin,NikolaiViktorovich
中科院分区:
--
文献类型:
--
作者:
Krutilina,RaisaIvanovna;Smirnova,AlexandraNikolaevna;Mudrak,OlgaStanislavovna;Pleskach,NadezhdaMikhailovna;Svetlova,MariaPavlovna;Oei,Shiao-Li;Yau,PeterM;Bradbury,EdwinMorton;Zalensky,AndreyOlegovich;Tomilin,NikolaiViktorovich

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中国仓鼠细胞具有大的间质(TTAGGG)带(IT),其不稳定,应通过未知机制进行保护。在此,我们在中国仓鼠V79细胞中表达了绿色荧光蛋白(GFP)标记的人TRF 1,并发现与IT结合的GFP-TRF 1的主要部分是扩散移动的。在用蛋白激酶抑制剂渥曼青霉素处理细胞后,这一比例大幅下降,并且这种药物还增加了染色体畸变的频率。电离辐射不会诱导GFP-TRF 1可检测的易位到使用抗组蛋白γ-H2 AX的抗体可视化的随机双链断裂位点。已知TRF 1通过过表达端锚聚合酶1从端粒中消除,端锚聚合酶1诱导TRF 1聚(ADP-核糖基)化。我们转染V79细胞的质粒编码端锚聚合酶1,并发现,在这些细胞中的染色体重排的频率增加,独立于他们的治疗IR。两者合计,我们的研究结果表明,TRF 1参与序列特异性保护内部非端粒(TTAGGG)n重复。
Chinese hamster cells have large interstitial (TTAGGG) bands (ITs) which are unstable and should be protected by an unknown mechanism. Here, we expressed in Chinese hamster V79 cells green fluorescent protein (GFP)-tagged human TRF1, and found that a major fraction of GFP-TRF1 bound to ITs is diffusionally mobile. This fraction strongly decreases after treatment of cells with wortmannin, a protein kinase inhibitor, and this drug also increases the frequency of chromosome aberrations. Ionizing radiation does not induce detectable translocation of GFP-TRF1 to the sites of random double-strand breaks visualized using antibodies against histone γ-H2AX. TRF1 is known to be eliminated from telomeres by overexpression of tankyrase 1 which induces TRF1 poly (ADP-ribosyl) ation. We transfected V79 cells by plasmid encoding tankyrase 1 and found that the frequency of chromosome rearrangements is increased in these cells independently of their treatment by IR. Taken together, our results suggest that TRF1 is involved in sequence-specific protection of internal nontelomeric (TTAGGG) n repeats.
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