A high-resolution, nanopore-based artificial intelligence assay for DNA replication stress in human cancer cells.

ABSTRACT: DNA replication stress is a hallmark of cancer that is exploited by chemotherapies. Current assays for replication stress have low throughput and poor resolution whilst being unable to map the movement of replication forks genome-wide. We present a new method that uses nanopore sequencing and artificial intelligence to map forks and measure their rates of movement and stalling in melanoma and colon cancer cells treated with chemotherapies. Our method can differentiate between fork slowing and fork stalling in cells treated with hydroxyurea, as well as inhibitors of ATR, WEE1, and PARP1. These different therapies yield different characteristic signatures of replication stress. We assess the role of the intra-S-phase checkpoint on fork slowing and stalling and show that replication stress dy

SUBMITTER: Jones MJK 

PROVIDER: S-EPMC12365011 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature