DNA damage response

The DNA damage response is a network of cellular pathways that detects DNA lesions and coordinates repair, cell-cycle arrest, senescence, or cell death.

ATM kinase: A protein kinase activated mainly by DNA double-strand breaks that coordinates checkpoint signaling and repair. It relays double-strand-break signals to checkpoint and repair proteins.
DNA damage: Alteration to DNA structure or sequence caused by chemical, physical, or biological agents. Lesions are the initiating signals that activate this response network.
BRCA1: A tumor-suppressor protein that helps coordinate DNA repair, especially homologous recombination. BRCA1 loss weakens accurate repair and creates therapeutic vulnerabilities.
Xeroderma pigmentosum: A group of inherited disorders marked by extreme ultraviolet sensitivity and high skin-cancer risk. The disease provided early evidence that cells require specific pathways to repair DNA lesions.
Cancer: A group of diseases in which abnormal cells grow and spread through uncontrolled proliferation. Accumulated mutations from failed damage control can drive cancer development.
ATR kinase: A protein kinase activated by replication stress and exposed single-stranded DNA. It signals replication problems that threaten genome integrity.
DNA double-strand break: A DNA lesion in which both strands of the double helix are broken near the same site. These severe lesions recruit dedicated sensors and repair pathways.
BRCA2: A tumor-suppressor protein that helps load RAD51 onto DNA during homologous recombination. BRCA2 deficiency links inherited cancer risk to defective break repair.
James Cleaver: A molecular biologist who linked defective nucleotide-excision repair to xeroderma pigmentosum. His work connected a human disease phenotype to defective cellular DNA repair.
Cellular senescence: A durable state in which a cell stops dividing while remaining metabolically active. Persistent damage can impose senescence, limiting proliferation while changing tissue signaling.

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