Ask about this productRelated genes to: ALKBH2 Blocking Peptide
- Gene:
- ALKBH2 NIH gene
- Name:
- alkB homolog 2, alpha-ketoglutarate dependent dioxygenase
- Previous symbol:
- -
- Synonyms:
- MGC90512, ABH2
- Chromosome:
- 12q24.11
- Locus Type:
- gene with protein product
- Date approved:
- 2006-02-09
- Date modifiied:
- 2019-03-26
Related products to: ALKBH2 Blocking Peptide
Related articles to: ALKBH2 Blocking Peptide
- AlkB-family Fe(II)/2-oxoglutarate-dependent dioxygenases repair alkylated nucleic acid lesions through oxidative dealkylation and play important roles in genome maintenance. 1-Methyl-2'-deoxyadenosine (1mA) and 3-methyl-2'-deoxycytidine (3mC) are well-established substrates of AlkB, ALKBH2, and ALKBH3. Although these enzymes have been extensively studied, the influence of proton concentration (pH) on their catalytic behavior and strand preference remains poorly defined. Here, we systematically examined how pH modulates the activity of the prototypical bacterial AlkB and the human homologues ALKBH2 and ALKBH3 using defined DNA substrates in both single-stranded (ssDNA) and double-stranded (dsDNA) contexts containing 1mA and 3mC lesions. Across a broad pH range, all three enzymes mainly exhibit bell-shaped activity profiles with distinct optima. The prevailing view in the field is that AlkB preferentially repairs these lesions in ssDNA, ALKBH2 favors dsDNA, and ALKBH3 prefers ssDNA. However, our results demonstrate that pH influences the catalytic efficiency and strand utilization in a substrate- and enzyme-dependent manner. AlkB maintains a consistent ssDNA preference for 3mC but exhibits variable strand preference for 1mA at different pH values. ALKBH2 retains a strong dsDNA preference for 1mA across all conditions but shows a clear pH-dependent strand switch for 3mC, favoring ssDNA under acidic conditions and preferring dsDNA at neutral to alkaline pH conditions. In contrast, ALKBH3 consistently favors ssDNA for 3mC but exhibits pH-dependent strand preference for 1mA. Our results show that the reported strand preferences largely hold at pH 7.0-8.0 but are not complete, as strand utilization and pH optima vary by enzyme and substrate. The observations demonstrate that proton availability strongly influences AlkB-family catalysis and is an important factor in how these enzymes process damaged DNA. These findings may also aid the optimization of AlkB-based protein engineering and sequencing technologies. - Source: PubMed
Publication date: 2026/06/08
Howarth Samuel DMylie Quentin JBoateng-Boakye EvansFalkowski VincentOliver Mella AmbarFermin RafaelPeng ZhiyuanBush XinChen Yi-TzaiMa JianCho BongsupLi Deyu - Profiling the spatiotemporal dynamics of DNA demethylases is critical for deciphering the mechanisms of epigenetic regulation and genomic maintenance. However, existing fluorescent strategies often suffer from false-positive signals in living cells, primarily arising from non-specific nuclease degradation or instability of the complex amplification components. Herein, we present a generalisable "demethylation-activated" fluorescent light-up DNA aptamer (FLAP) strategy for high-contrast imaging of DNA alkylation repair in living cells. Our design relies on a precise "caging" strategy: site-specific methyl lesions (, O-meG) are engineered into the ligand-binding domain of the Bibb Lettuce aptamer, which disrupts its folding and suppresses fluorescence. Upon specific enzymatic repair, the aptamer structure is restored, triggering a robust fluorescence "turn-on" signal. This mechanism effectively minimises false-positive signals. The optimised probe detects MGMT activity with high sensitivity (LOD: 1.64 nM) and enables direct visualisation of active demethylation processes in MCF-7 cells, revealing distinct responses to inhibitors. Highlighting the modularity of the platform, we extended the design to detect AlkBH2 (LOD: 0.81 nM) simply by substituting the lesion with 1-methyladenine (1-meA). This work establishes a versatile and programmable framework for converting transient DNA repair events into quantifiable optical signals, providing a powerful tool for exploring epigenetic dynamics and cancer pharmacology. - Source: PubMed
Publication date: 2026/05/28
Luan XinyuZhang HanLi ZheMa MiaoZhang JunruiLiu FangZhai JunqiuLuan Tiangang - A close relationship exists between inflammation and cancer. Recent studies have highlighted inflammation as a significant contributor to the progression of bladder cancer. However, the role of alkyladenine DNA glycosylase homolog 2 (AlkBH2), an enzyme involved in DNA repair and a member of the AlkB family, in the context of bladder cancer inflammation remains largely unexplored. Our findings demonstrate that AlkBH2 promotes the proliferation, colony formation, migration, and invasion of bladder cancer cells. Mechanistically, AlkBH2 activates the nuclear factor-kappa B (NF-κB) signaling pathway, which in turn drives the progression of bladder cancer. These results suggest that AlkBH2 plays a critical oncogenic role in bladder cancer by modulating inflammation through the activation of the NF-κB pathway. These findings highlight the potential of AlkBH2 as a therapeutic target for bladder cancer treatment. - Source: PubMed
Publication date: 2026/05/07
Yang ZhangjieMa JinhuQiang ZiyangXie WenhaoJiao LiangChen Guojun - Our laboratory has established that the free radical signaling molecule nitric oxide (NO) is an endogenous regulator of epigenetic methylation through direct inhibition of the Fe(II)/2-oxoglutarate-dependent dioxygenase (2-ODD) family, including histone demethylases (KDMs)[1, 2], mRNA demethylases (FTO, ALKBH5) [3], and DNA demethylases (TETs, ALKBH2) [4]. We previously showed that NO alters 38 histone post-translational modifications (PTMs) and genome-wide transcription in breast cancer cells [3]. Here, we comprehensively quantify 76 histone modifications, including 30 combinatorial marks on adjacent residues not resolved in the original analysis, and systematically profile methyl-modifying enzyme expression. We identify four coordinated histone PTM axes converging on a chromatin compaction signature: (i) H3K9 methylation accumulation with selective K9me1K14ac remodeling, (ii) H4K20me1→me2/me3 conversion, (iii) a novel H3K27-K36 combinatorial landscape shift, and (iv) preferential depletion of hyperacetylated H4 species. A composite Chromatin Compaction Score integrating all 76 PTMs with literature-based valence assignments confirms progressive compaction, validated independently by PCA. ChIP-seq reanalysis reveals that H3K9me2 accumulates predominantly at intergenic regions while K9ac undergoes activity-dependent redistribution governed by baseline chromatin state, with near-perfect reciprocal H3K9me2 gain at silent loci. Systematic enzyme profiling shows coordinated upregulation of 13/18 detected KDMs alongside methyltransferase downregulation, a compensatory response that fails to overcome direct enzymatic inhibition by NO. This compaction signature is associated with tumor-permissive gene silencing: DNA repair genes are downregulated, chromatin remodeling complexes suppressed, and IDH1 downregulation creates a feed-forward loop compounding 2-ODD inhibition. These findings establish NO-mediated KMD inhibition as a driver of coordinated chromatin compaction linked to pro-tumorigenic gene silencing. - Source: PubMed
Publication date: 2026/04/15
Shayan SaraVasudevan DivyaThomas Douglas D - This study aims to explore the potential molecular mechanisms by which di (2-ethylhexyl) phthalate (DEHP) exposure induces pulmonary arterial hypertension (PAH). - Source: PubMed
Publication date: 2026/03/20
Li HuaJiang YingchunLi Jijia