Vanguard is a Glucose Deprivation-Responsive Long Non-Coding RNA Essential for Chromatin Remodeling-Reliant DNA Repair.
Vanguard is a Glucose Deprivation-Responsive Long Non-Coding RNA Essential for Chromatin Remodeling-Reliant DNA Repair.
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DOI：
10.1002/advs.202201210
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发表时间：
2022-10
期刊：
影响因子：
15.1
通讯作者：
Liu, Lianxin
中科院分区：
文献类型：
--
作者：
Zhang, Ben;Thorne, Rick Francis;Zhang, Pengfei;Wu, Mian;Liu, Lianxin
葡萄糖代谢通过调节染色质重塑、双链断裂（DSB）修复和氧化还原稳态来促进DNA损伤反应途径，尽管其潜在机制尚未完全确立。在这里，揭示了一种以前未表征的长非编码RNA，称为Vanguard，其作用是促进与全局染色质可及性变化相关的HMGB 1依赖性DNA修复。根据葡萄糖的利用率和细胞三磷酸腺苷（ATP）水平，通过SP1依赖性转录在癌细胞中维持Vanguard表达。Vanguard促进HMGB 1和HDAC 1之间的复合物形成，从而使HMGB 1脱乙酰化，以维持其核定位和DSB修复功能。然而，在葡萄糖限制条件下，Vanguard下调促进HMGB 1从细胞核易位，增加DNA损伤，并损害癌细胞生长和活力。此外，Vanguard沉默增加了聚（ADP-核糖）聚合酶抑制剂对具有野生型乳腺癌基因-1状态的乳腺癌细胞的有效性，表明Vanguard是潜在的治疗靶点。一种以前未表征的长非编码RNA先锋，对葡萄糖剥夺有反应，对DNA修复至关重要。Vanguard从根本上促进HMGB 1和HDAC 1之间的复合物形成，从而使HMGB 1脱乙酰化，以维持HMGB 1的核定位和双链断裂修复功能。
Glucose metabolism contributes to DNA damage response pathways by regulating chromatin remodeling, double‐strand break (DSB) repair, and redox homeostasis, although the underlying mechanisms are not fully established. Here, a previously uncharacterized long non‐coding RNA is revealed that is call Vanguard which acts to promote HMGB1‐dependent DNA repair in association with changes in global chromatin accessibility. Vanguard expression is maintained in cancer cells by SP1‐dependent transcription according to glucose availability and cellular adenosine triphosphate (ATP) levels. Vanguard promotes complex formation between HMGB1 and HDAC1, with the resulting deacetylation of HMGB1 serving to maintain its nuclear localization and DSB repair function. However, Vanguard downregulation under glucose limiting conditions promotes HMGB1 translocation from the nucleus, increasing DNA damage, and compromising cancer cell growth and viability. Moreover, Vanguard silencing increases the effectiveness of poly (ADP‐ribose) polymerase inhibitors against breast cancer cells with wild‐type breast cancer gene‐1 status, suggesting Vanguard as a potential therapeutic target. A previously uncharacterized long non‐coding RNA Vanguard, responds to glucose deprivation and is essential for DNA repair. Vanguard fundamentally acts to promote complex formation between HMGB1 and HDAC1, with the resulting deacetylation of HMGB1 serving to maintain the nuclear localization and double‐strand break repair function of HMGB1.
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