The Architectural Chromatin Factor High Mobility Group A1 Enhances DNA Ligase IV Activity Influencing DNA Repair.
The Architectural Chromatin Factor High Mobility Group A1 Enhances DNA Ligase IV Activity Influencing DNA Repair.
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DOI：
10.1371/journal.pone.0164258
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Manfioletti G
中科院分区：
文献类型：
--
作者：
Pellarin I;Arnoldo L;Costantini S;Pegoraro S;Ros G;Penzo C;Triolo G;Demarchi F;Sgarra R;Vindigni A;Manfioletti G
HMGA 1结构转录因子是在绝大多数人类癌症中过表达的癌基因。HMGA 1是核分子网络中高度连接的节点，HMGA 1参与癌症发展的关键方面是HMGA 1同时赋予细胞多种致癌作用，范围从整体染色质结构和基因表达修饰到关键细胞蛋白的直接功能改变。有趣的是，HMGA 1还调节DNA损伤修复途径。在这项工作中，我们提供了证据连接HMGA 1与非同源末端连接DNA修复。我们表明，HMGA 1是在复杂的，是一个底物的DNA-PK。HMGA 1增强连接酶IV活性，并抵消组蛋白H1对DNA末端连接的抑制活性。此外，过表达HMGA 1的乳腺癌细胞在诱导DNA双链断裂后显示出更快的恢复，这与更高的存活率相关。这些数据表明，癌细胞对DNA损伤剂的耐药性可能部分归因于HMGA 1过表达，因此突出了在选择有价值和有效的药理学方案时考虑HMGA 1表达水平的相关性。
The HMGA1 architectural transcription factor is an oncogene overexpressed in the vast majority of human cancers. HMGA1 is a highly connected node in the nuclear molecular network and the key aspect of HMGA1 involvement in cancer development is that HMGA1 simultaneously confers cells multiple oncogenic hits, ranging from global chromatin structural and gene expression modifications up to the direct functional alterations of key cellular proteins. Interestingly, HMGA1 also modulates DNA damage repair pathways. In this work, we provide evidences linking HMGA1 with Non-Homologous End Joining DNA repair. We show that HMGA1 is in complex with and is a substrate for DNA-PK. HMGA1 enhances Ligase IV activity and it counteracts the repressive histone H1 activity towards DNA ends ligation. Moreover, breast cancer cells overexpressing HMGA1 show a faster recovery upon induction of DNA double-strand breaks, which is associated with a higher survival. These data suggest that resistance to DNA-damaging agents in cancer cells could be partially attributed to HMGA1 overexpression thus highlighting the relevance of considering HMGA1 expression levels in the selection of valuable and effective pharmacological regimens.
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影响因子：
82.9
作者：
Foti, D;Chiefari, E;Brunetti, A
通讯作者：
Brunetti, A
影响因子：
5.3
作者：
Baldassarre, G;Battista, S;Fusco, A
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Fusco, A
影响因子：
50.3
作者：
Fedele, Monica;Visone, Rosa;Fusco, Alfredo
通讯作者：
Fusco, Alfredo
影响因子：
11.2
作者：
Fedele, M;Fidanza, V;Fusco, A
通讯作者：
Fusco, A
影响因子：
11.2
作者：
Adair, Jennifer E.;Maloney, Scott C.;Reeves, Raymond
通讯作者：
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