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Publicly Accessible Penn Dissertations

ATR

Genetics and Genomics

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Full-Text Articles in Molecular Biology

Dissecting The Functions Of Atr In Replication Fork Stability, Theonie Anastassiadis Jan 2017

Dissecting The Functions Of Atr In Replication Fork Stability, Theonie Anastassiadis

Publicly Accessible Penn Dissertations

Genome maintenance is required for cellular viability, and failure to preserve genomic integrity is associated with an increased risk of diseases, such as cancer. To ensure genomic stability, cells have checkpoints that control cell cycle progression in the event of DNA damage or incomplete DNA replication. The DNA replication checkpoint is regulated by the ATR-CHK1 pathway that stabilizes stalled replication forks and prevents their collapse into DNA double-strand breaks (DSBs). Two distinct models have been proposed to explain how ATR stabilizes stalled forks: 1) through local modulation of fork remodelers, such as SMARCAL1 inhibition, and 2) through inhibition of CDK-dependent ...