DNA-PKcs phosphorylates hnRNP-A1 to facilitate the RPA-to-POT1 switch and telomere capping after replication.
DNA-PKcs phosphorylates hnRNP-A1 to facilitate the RPA-to-POT1 switch and telomere capping after replication.
复制标题
DNA-PKcs 磷酸化 hnRNP-A1，以促进复制后 RPA 至 POT1 的转换和端粒加帽
DOI：
10.1093/nar/gkv539
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发表时间：
2015-07-13
影响因子：
14.9
通讯作者：
Chen BP
中科院分区：
文献类型：
--
作者：
Sui J;Lin YF;Xu K;Lee KJ;Wang D;Chen BP
异质性核糖核蛋白A1(hnRNP-A1)与端粒保护和端粒酶激活有关。最近的证据进一步表明，hnRNP-A1在维持新复制的端粒3‘端悬挑和促进从复制蛋白A(RPA)到保护端粒1(POT1)的转换中起着至关重要的作用。HnRNP-A1在端粒保护中的作用还涉及DNA依赖的蛋白激酶催化亚单位(DNA-PKcs)，尽管具体的调控机制尚不清楚。在这里，我们报告了hnRNP-A1在G2和M期被DNA-PKcs磷酸化，并且DNA-PK依赖的hnRNP-A1磷酸化促进了端粒单链3‘端悬挑上的RPA到POT1的开关。因此，在缺乏hnRNP-A1或DNA-PKcs依赖的hnRNP-A1磷酸化的细胞中，RPA到POT1的开关受损导致有丝分裂过程中端粒的DNA损伤反应，并诱导脆弱的端粒。综上所述，我们的结果表明，依赖DNA-PKcs的hnRNP-A1磷酸化对于新复制的端粒的封顶和防止端粒异常至关重要。
The heterogeneous nuclear ribonucleoprotein A1 (hnRNP-A1) has been implicated in telomere protection and telomerase activation. Recent evidence has further demonstrated that hnRNP-A1 plays a crucial role in maintaining newly replicated telomeric 3′ overhangs and facilitating the switch from replication protein A (RPA) to protection of telomeres 1 (POT1). The role of hnRNP-A1 in telomere protection also involves DNA-dependent protein kinase catalytic subunit (DNA-PKcs), although the detailed regulation mechanism has not been clear. Here we report that hnRNP-A1 is phosphorylated by DNA-PKcs during the G2 and M phases and that DNA-PK-dependent hnRNP-A1 phosphorylation promotes the RPA-to-POT1 switch on telomeric single-stranded 3′ overhangs. Consequently, in cells lacking hnRNP-A1 or DNA-PKcs-dependent hnRNP-A1 phosphorylation, impairment of the RPA-to-POT1 switch results in DNA damage response at telomeres during mitosis as well as induction of fragile telomeres. Taken together, our results indicate that DNA-PKcs-dependent hnRNP-A1 phosphorylation is critical for capping of the newly replicated telomeres and prevention of telomeric aberrations.
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DOI：
10.1126/science.1170633
发表时间：
2009-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
de Lange T
通讯作者：
de Lange T
DOI：
10.1007/s00018-008-8532-1
发表时间：
2009-04
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
He Y;Smith R
通讯作者：
Smith R
影响因子：
10.5
作者：
Mordes, Daniel A.;Glick, Gloria G.;Cortez, David
通讯作者：
Cortez, David
影响因子：
14.9
作者：
Redon S;Zemp I;Lingner J
通讯作者：
Lingner J
影响因子：
4.8
作者：
Bianchi, A;de Lange, T
通讯作者：
de Lange, T