Non-erythroid alpha spectrin prevents telomere dysfunction after DNA interstrand cross-link damage.
Non-erythroid alpha spectrin prevents telomere dysfunction after DNA interstrand cross-link damage.
复制标题
DOI：
10.1093/nar/gkt235
复制
发表时间：
2013-05-01
影响因子：
14.9
通讯作者：
Lambert MW
中科院分区：
文献类型：
--
作者：
Zhang P;Herbig U;Coffman F;Lambert MW
端粒完整性对端粒功能和基因组稳定性至关重要。我们先前证明，非红细胞α-血影蛋白（αIISp）存在于哺乳动物细胞核中，在DNA链间交联（ICL）和染色体稳定性的修复中起重要作用。我们现在证明αIISp对ICL损伤后端粒的维持也很重要。它定位于ICL损伤后S期的端粒，在那里它增强了与TRF 1和TRF 2的关联，并且是ICL修复蛋白XPF募集到端粒处损伤诱导的病灶所必需的。在通过siRNA去除αIISp的端粒酶阳性正常细胞中或在范可尼贫血、互补组A（FA-A）细胞中，其中αIISp水平为正常的35-40%，ICL损伤导致XPF无法定位于端粒，显著增加端粒功能障碍诱导的病灶，随后是端粒的灾难性损失。在FA-A细胞中αIISp水平恢复至正常可纠正这些缺陷。我们的研究表明，αIISp对端粒DNA ICL的修复至关重要，可能是通过促进修复蛋白的募集，与其在基因组DNA中修复DNA ICL的作用相似，但不相同，并且这种功能反过来对DNA ICL损伤后的端粒维持至关重要。
Telomere integrity is critical for telomere function and genomic stability. We previously demonstrated that non-erythroid α-spectrin (αIISp) is present in mammalian cell nuclei where it is important in repair of DNA interstrand cross-links (ICLs) and chromosome stability. We now demonstrate that αIISp is also important for telomere maintenance after ICL damage. It localizes to telomeres in S phase after ICL damage where it has enhanced association with TRF1 and TRF2 and is required for recruitment of the ICL repair protein, XPF, to damage-induced foci at telomeres. In telomerase-positive normal cells depleted of αIISp by siRNA or in Fanconi anemia, complementation group A (FA-A) cells, where αIISp levels are 35–40% of normal, ICL damage results in failure of XPF to localize to telomeres, markedly increased telomere dysfunction-induced foci, followed by catastrophic loss of telomeres. Restoration of αIISp levels to normal in FA-A cells corrects these deficiencies. Our studies demonstrate that αIISp is critical for repair of DNA ICLs at telomeres, likely by facilitating the recruitment of repair proteins similar, but not identical, to its proposed role in repair of DNA ICLs in genomic DNA and that this function in turn is critical for telomere maintenance after DNA ICL damage.
登录
查看更多内容
影响因子：
16.8
作者：
通讯作者：
--
影响因子：
14.9
作者：
Al-Minawi AZ;Lee YF;Håkansson D;Johansson F;Lundin C;Saleh-Gohari N;Schultz N;Jenssen D;Bryant HE;Meuth M;Hinz JM;Helleday T
通讯作者：
Helleday T
影响因子：
5.3
作者：
Akkari, YMN;Bateman, RL;Grompe, M
通讯作者：
Grompe, M
影响因子：
16
作者：
Garcia-Higuera, I;Taniguchi, T;D'Andrea, AD
通讯作者：
D'Andrea, AD
影响因子：
4.8
作者：
Ballal, Rahul D.;Saha, Tapas;Rosen, Eliot M.
通讯作者：
Rosen, Eliot M.