RAD17

Overview

RAD17 (RAD17 checkpoint clamp loader component) is a key component of the DNA damage checkpoint pathway. It loads the RAD9-RAD1-HUS1 (9-1-1) clamp onto DNA at sites of damage and is required for proper ATR-mediated checkpoint activation. Mutations that disrupt RAD17 function impair DNA damage sensing and may contribute to genomic instability and hypermutation.

Alterations observed in the corpus

  • Nonsense mutations observed in NSCLC tumors from pembrolizumab-treated patients; required for proper DNA damage response; found in DCB patients in a cohort where high mutation burden predicts benefit from anti-PD-1 therapy PMID:25765070

Cancer types (linked)

  • NSCLC: Nonsense mutations in pembrolizumab-treated cohort; observed in DCB patients PMID:25765070

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • Defective DNA damage response via RAD17 loss may contribute to elevated tumor mutation burden, which predicts durable clinical benefit from pembrolizumab in NSCLC PMID:25765070

Open questions

Sources

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