Vanguard is a Glucose Deprivation‐Responsive Long Non‐Coding RNA Essential for Chromatin Remodeling‐Reliant DNA Repair. Issue 30 (1st September 2022)

• Record Type: Journal Article
• Authors: Zhang, Ben; Thorne, Rick Francis; Zhang, Pengfei; Wu, Mian; Liu, Lianxin
• Is Part Of: Advanced science. Volume 9:Issue 30(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-09-01
• Subjects: genomic stability -- HMGB1 -- long non‐coding RNAs -- PARP inhibitors -- Vanguard; Science -- Periodicals; 505
• DOI: 10.1002/advs.202201210
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: 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. Abstract : 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.