ATP-dependent DNA damage sensor activity

Definition

Target type: molecularfunction

A molecule that recognises toxic DNA structures, and initiates a signaling response, driven by ATP hydrolysis. [PMID:33302090, PMID:33510387]

ATP-dependent DNA damage sensor activity is a crucial molecular function in maintaining genomic integrity. It involves proteins that use the energy from ATP hydrolysis to detect and bind to damaged DNA. These proteins are often the first responders to DNA damage, acting as sentinels that initiate downstream signaling pathways and repair mechanisms.

Here is a detailed description of the process:

1. **ATP Binding and Hydrolysis:** The sensor proteins possess specific ATP-binding domains. Upon encountering damaged DNA, these domains bind ATP, and the energy derived from ATP hydrolysis fuels the protein's conformational changes and interaction with the damaged DNA.

2. **Damage Recognition and Binding:** The sensor proteins exhibit high affinity for various DNA damage types, including double-strand breaks (DSBs), single-strand breaks (SSBs), bulky adducts, and base modifications. Their ability to recognize and bind to these lesions is often facilitated by structural changes induced by ATP hydrolysis.

3. **Signal Transduction:** Once bound to damaged DNA, the sensor proteins activate downstream signaling pathways. This involves recruiting other repair factors, such as kinases, ubiquitin ligases, and nucleases, to the damage site. The activation of these pathways is often regulated by post-translational modifications, like phosphorylation or ubiquitination.

4. **Repair Pathway Initiation:** The sensor proteins play a crucial role in determining the specific repair pathway that will be employed. Depending on the nature and location of the damage, they can initiate different repair mechanisms, such as nucleotide excision repair (NER), base excision repair (BER), or homologous recombination (HR).

5. **Checkpoint Activation:** In some cases, the sensor proteins can trigger cell cycle checkpoints, halting cell division until the damage is repaired. This ensures that damaged DNA is not replicated, preventing the accumulation of mutations and genomic instability.

Overall, ATP-dependent DNA damage sensor activity is a complex and highly regulated process. It is essential for maintaining the integrity of the genome, preventing mutations, and ensuring cell viability. Mutations in these sensor proteins can lead to various genetic disorders and increased cancer risk.'
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Proteins (1)

Compounds (4)