GO:0008094 ATP-dependent activity, acting on DNA: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0008094 (ATP-dependent activity, acting on DNA) describes catalytic activities that modify DNA using energy from ATP hydrolysis.
• This term covers DNA-dependent ATPases and chromatin-remodeling ATPases that translocate along DNA or nucleosomes.
• Representative enzymes include reverse gyrase, which possesses intrinsic DNA-dependent ATPase activity, and ATP-dependent chromatin remodelers such as the BAF complex.
• These activities are essential for nucleosome eviction, transcription factor access, and genome integrity [1,3].
• Dysregulation of ATP-dependent DNA transactions is linked to cancer and neurological disorders [6,8].
• CRISPR-based knockout, point mutation, knock-in, and overexpression models enable functional dissection of these enzymes [1,3].
Description
GO:0008094, ATP-dependent activity, acting on DNA, is a molecular function term that captures catalytic activities which modify DNA in an ATP-hydrolysis-dependent manner. This includes DNA-dependent ATPases and ATP-driven chromatin remodelers that use the energy of ATP to translocate along DNA, disrupt nucleosome contacts, or otherwise alter DNA structure. The term is fundamental because many essential nuclear processes, such as transcription, replication, and DNA repair, rely on enzymes that convert chemical energy into mechanical work on DNA [1,4]. For researchers, GO:0008094 provides a unified annotation for diverse proteins that share a common mechanistic feature: ATP binding and hydrolysis coupled to DNA interaction. Understanding this activity is critical for interpreting how cells regulate chromatin architecture and maintain genome stability [1,3].
ATP-dependent activity, acting on DNA At A Glance
| GO ID | GO:0008094 |
|---|---|
| GO term | ATP-dependent activity, acting on DNA |
| Ontology | molecular_function |
| Synonym | DNA-dependent ATPase activity; ATPase, acting on DNA; adenosinetriphosphatase (DNA-dependent) |
| Major function | Catalytic modification of DNA driven by ATP hydrolysis |
| Cellular context | Nucleus, chromatin, and DNA metabolic machines |
| Representative enzymes | Reverse gyrase, chromatin-remodeling ATPases (e.g., BAF complex subunits) |
| Related processes | Nucleosome remodeling, transcription regulation, DNA repair, genome stability |
What Is GO:0008094?
According to the Gene Ontology, GO:0008094 is defined as catalytic activity that acts to modify DNA, driven by ATP hydrolysis. In other words, it is a molecular function in which the energy released by ATP hydrolysis is used to change DNA or its associated structures, such as nucleosomes.
Why Is ATP-dependent activity, acting on DNA Important in Cell Biology?
GO:0008094 is important because ATP-dependent DNA-modifying activities are central to chromatin dynamics and genome maintenance [1,4]. Chromatin remodelers such as the BAF complex use ATP hydrolysis to evict nucleosomes and regulate transcription factor access, directly influencing gene expression programs [1,3]. In addition, enzymes like reverse gyrase demonstrate intrinsic DNA-dependent ATPase activity that is critical for their function in extreme environments. Disruption of these activities can lead to aberrant transcription, genomic instability, and disease, making them attractive targets for therapeutic intervention and functional genomics [6,8].
• Enables nucleosome eviction and chromatin accessibility for transcription.
• Supports transcription factor access to chromatin through remodeler activity.
• Provides mechanistic basis for ATP-dependent chromatin remodeling.
• Contributes to genome integrity via DNA repair and resolution of DNA lesions.
• Involved in proofreading and fidelity of DNA replication.
• Linked to cancer biology, including colorectal cancer and anaphase-promoting complex regulation.
• Associated with neurological disorders such as those involving aprataxin deficiency.
• Essential for reverse gyrase function in thermophilic organisms.
• Target for CRISPR-based functional studies of chromatin remodelers [1,3].
• Guides development of small-molecule inhibitors targeting ATPase domains.
What Happens During ATP-dependent activity, acting on DNA?
ATP Binding and DNA Engagement
In simple terms: The enzyme first grabs ATP and binds to DNA.
The catalytic cycle begins with ATP binding to the ATPase domain of the enzyme, followed by engagement with DNA or nucleosomal DNA. This step is often regulated by accessory subunits and post-translational modifications.
ATP Hydrolysis and Conformational Change
In simple terms: ATP is split, causing the enzyme to change shape.
Hydrolysis of ATP to ADP and inorganic phosphate induces conformational changes in the enzyme, which are coupled to mechanical work on DNA. For example, reverse gyrase exhibits intrinsic DNA-dependent ATPase activity that drives DNA supercoiling.
DNA Modification or Nucleosome Remodeling
In simple terms: The enzyme moves or alters DNA structure.
The energy from ATP hydrolysis is used to translocate along DNA, evict nucleosomes, or remodel chromatin. The BAF chromatin remodeler synergizes with RNA polymerase II and transcription factors to evict nucleosomes. Similarly, ChAHP remodeling activity restricts transcription factor access to chromatin.
Product Release and Reset
In simple terms: The enzyme lets go and can start again.
After DNA modification, ADP and inorganic phosphate are released, and the enzyme returns to its initial state, ready for another cycle. This cycle is essential for dynamic chromatin regulation and DNA metabolism [1,3].
Key Genes Involved in GO:0008094 ATP-dependent activity, acting on DNA
The following genes encode proteins with ATP-dependent activity acting on DNA, as supported by published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SMARCA4 (BRG1) | ATPase subunit of BAF chromatin remodeler | Nucleosome eviction and transcription regulation |
| SMARCA2 (BRM) | ATPase subunit of BAF remodeler | Chromatin remodeling in development and cancer |
| CHD4 | ATP-dependent chromatin remodeler | Nucleosome remodeling and transcription repression |
| CHD3 | ATP-dependent chromatin remodeler | Chromatin accessibility regulation |
| ADNP | ChAHP complex subunit with remodeler activity | Restricts transcription factor access |
| HP1BP3 | ChAHP complex component | Chromatin remodeling and transcription regulation |
| TOP2A | DNA topoisomerase II | ATP-dependent DNA cleavage and rejoining |
| TOP2B | DNA topoisomerase II beta | ATP-dependent DNA transactions in neurons |
| APTX | Aprataxin, resolves adenylated RNA-DNA junctions | Genome integrity and neurodegeneration |
| POL3 (DNA polymerase III) | Replication proofreading | ATP-dependent proofreading activity |
| REV1 | Translesion synthesis polymerase | ATP-dependent DNA damage bypass |
| RAD54 | ATP-dependent DNA translocase | Homologous recombination and repair |
| SMARCAL1 | ATP-dependent annealing helicase | Replication fork stability |
| ERCC6 (CSB) | ATP-dependent DNA translocase | Transcription-coupled repair |
| ERCC8 (CSA) | ATP-dependent repair factor | Cockayne syndrome and DNA repair |
| ATRX | ATP-dependent chromatin remodeler | Telomere maintenance and chromatin regulation |
| DAXX | ATP-dependent chromatin assembly | Histone H3.3 deposition |
How Is ATP-dependent activity, acting on DNA Regulated?
ATP-dependent activity acting on DNA is regulated at multiple levels. Accessory subunits and transcription factors can modulate the recruitment and activity of chromatin remodelers such as the BAF complex. Post-translational modifications of remodeler subunits influence their ATPase activity and targeting. Additionally, the availability of ATP and the presence of specific DNA structures, such as adenylated RNA-DNA junctions, can regulate enzyme activity. In some cases, auxiliary subunits of DNA polymerase III modulate proofreading activity, which responds like elongation activity to these subunits.
ATP-dependent activity, acting on DNA and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SMARCA4 | Cancer (e.g., lung, ovarian) | Knockout and point mutation in cancer cell lines |
| APTX | Neurodegeneration (ataxia-oculomotor apraxia) | Knock-in of patient mutations in iPSCs |
| ANAPC1 | Colorectal cancer | Overexpression and knockout in colorectal cancer models |
| ERCC6 | Cockayne syndrome | Knockout in fibroblasts and neuronal cells |
| TOP2A | Cancer and chemoresistance | Point mutation of ATPase domain |
Cancer
Dysregulation of ATP-dependent chromatin remodelers is frequently observed in cancer. For example, the anaphase-promoting complex subunit 1 (ANAPC1) has potential biological roles and clinical significance in colorectal cancer, and its function may intersect with ATP-dependent DNA transactions. Mutations in BAF complex subunits such as SMARCA4 are associated with various malignancies.
Neurodegeneration
Aprataxin (APTX) resolves adenylated RNA-DNA junctions to maintain genome integrity, and its deficiency leads to neurodegenerative disease. This highlights the importance of ATP-dependent DNA processing in neuronal survival.
Genome Instability Syndromes
Defects in ATP-dependent DNA repair and remodeling factors, such as those involved in transcription-coupled repair, can cause genome instability syndromes characterized by developmental abnormalities and cancer predisposition.
From ATP-dependent activity, acting on DNA-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does SMARCA4 ATPase activity drive nucleosome eviction? | Point mutation (ATPase-dead) knock-in |
| What is the role of APTX in genome integrity? | Knockout and knock-in of patient mutations |
| How does ANAPC1 overexpression affect colorectal cancer? | Overexpression in cancer cell lines |
| Is CHD4 required for transcription factor restriction? | Knockout in stem cells |
| Can reverse gyrase ATPase activity be uncoupled from supercoiling? | Point mutation in thermophilic bacteria |
| What is the effect of BAF complex loss on transcription? | Knockout of SMARCA4 in mouse models |
How to Study the ATP-dependent activity, acting on DNA Process
| Method | What It Measures | Typical Application |
|---|---|---|
| ATPase assay | ATP hydrolysis rate | Enzyme kinetics of DNA-dependent ATPases |
| ATAC-seq | Chromatin accessibility | Nucleosome eviction by remodelers |
| MNase-seq | Nucleosome positioning | Chromatin remodeling activity |
| CRISPR knockout | Gene function loss | Causal role of ATP-dependent enzymes |
| CRISPR point mutation | Specific domain function | ATPase-dead mutants |
| ChIP-seq | Protein-DNA binding | Remodeler localization |
| Proteomics | Protein interactions | Complex composition |
| In vitro remodeling | Nucleosome sliding | Mechanistic studies |
ATPase Assays
Direct measurement of ATP hydrolysis in the presence of DNA can quantify DNA-dependent ATPase activity. This is exemplified by studies on reverse gyrase, which exhibits intrinsic DNA-dependent ATPase activity.
Chromatin Accessibility Assays
ATAC-seq and MNase-seq can assess nucleosome positioning and chromatin accessibility changes upon modulation of ATP-dependent remodelers [1,3].
Genome Editing and Functional Genomics
CRISPR knockout and point mutation models allow causal testing of specific ATPase domains in DNA transactions [1,8].
Biochemical Reconstitution
Purified proteins and nucleosomes can be used to reconstitute ATP-dependent remodeling and measure kinetics.
How CRISPR Can Be Used to Study GO:0008094 ATP-dependent activity, acting on DNA
Knockout
CRISPR knockout of genes encoding ATP-dependent DNA enzymes, such as SMARCA4, can reveal their essential roles in nucleosome eviction and transcription. Knockout models are also used to study APTX in genome integrity.
Point Mutation
Introducing point mutations in the ATPase domain (e.g., Walker A or B motifs) allows separation of ATP hydrolysis from DNA binding, as demonstrated for chromatin remodelers.
Knock-in
Knock-in of patient-derived mutations, such as those in APTX, can model neurodegenerative disease and assess DNA repair defects.
Overexpression
Overexpression of ATP-dependent DNA enzymes, such as ANAPC1, can drive oncogenic phenotypes and is used to study colorectal cancer.
How EDITGENE Supports ATP-dependent activity, acting on DNA Research
Researchers studying ATP-dependent activity, acting on DNA-related genes often need to determine whether a candidate gene is causally involved in chromatin remodeling, DNA repair, or disease. EDITGENE provides comprehensive CRISPR services to generate precisely engineered cell models for such functional studies.
Contact EDITGENE today to design your custom CRISPR model for ATP-dependent activity, acting on DNA research.
Frequently Asked Questions About ATP-dependent activity, acting on DNA
What is GO:0008094?
GO:0008094 is a Gene Ontology molecular function term for ATP-dependent activity, acting on DNA, defined as catalytic activity that modifies DNA driven by ATP hydrolysis.
What genes are involved in ATP-dependent activity, acting on DNA?
Genes include SMARCA4, SMARCA2, CHD4, APTX, and ANAPC1, among others [1,3,6,8].
How is ATP-dependent chromatin remodeling studied?
Common methods include ATPase assays, ATAC-seq, MNase-seq, and CRISPR knockout models [1,2,3].
What diseases are linked to ATP-dependent DNA enzymes?
They are linked to cancer, neurodegeneration, and genome instability syndromes [6,8].
What is the role of reverse gyrase in ATP-dependent DNA activity?
Reverse gyrase has intrinsic DNA-dependent ATPase activity that drives DNA supercoiling.
How does the BAF complex use ATP?
The BAF complex uses ATP hydrolysis to evict nucleosomes and regulate transcription.
Can CRISPR be used to study ATP-dependent DNA activity?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are widely used [1,4,8].
What is the difference between ATP-dependent activity and ATPase activity?
GO:0008094 specifically requires DNA as the substrate for modification, whereas general ATPase activity may act on other substrates.
Which experimental models are suitable for studying APTX?
Knockout and knock-in models in iPSCs or cell lines are suitable for studying APTX function.
How does ANAPC1 relate to colorectal cancer?
ANAPC1 has potential biological roles and clinical significance in colorectal cancer, and its overexpression may promote tumorigenesis.
Conclusion
GO:0008094 ATP-dependent activity, acting on DNA represents a crucial molecular function that underpins chromatin dynamics, DNA repair, and genome stability. The integration of biochemical assays, CRISPR-based models, and genomic technologies continues to illuminate the mechanisms and disease relevance of these enzymes [1,4,8]. Targeting ATP-dependent DNA activities holds promise for therapeutic development in cancer and neurodegeneration [6,8].
References
- 1. Brahma S et al.. 2024. The BAF chromatin remodeler synergizes with RNA polymerase II and transcription factors to evict nucleosomes.. Nat Genet 56(1):100-111 PMID: 38049663
- 2. Shibata T et al.. 1987. Intrinsic DNA-dependent ATPase activity of reverse gyrase.. J Biol Chem 262(22):10419-21 PMID: 3038879
- 3. Ahel J et al.. 2026. Remodeling activity of ChAHP restricts transcription factor access to chromatin.. Mol Cell 86(14):2754-2764.e9 PMID: 42413491
- 4. Flaus A et al.. 2001. Mechanisms for ATP-dependent chromatin remodelling.. Curr Opin Genet Dev 11(2):148-54 PMID: 11250137
- 6. Chen Y et al.. 2025. The Potential Biological Roles and Clinical Significance of Anaphase-Promoting Complex Subunit 1 in Colorectal Cancer.. Cancer Control 32:10732748251330059 PMID: 40229946
- 7. Reems JA et al.. 1991. Proofreading activity of DNA polymerase III responds like elongation activity to auxiliary subunits.. J Biol Chem 266(8):4878-82 PMID: 2002034
- 8. Tumbale P et al.. 2014. Aprataxin resolves adenylated RNA-DNA junctions to maintain genome integrity.. Nature 506(7486):111-5 PMID: 24362567
