ATR inhibition radiosensitizes cells through augmented DNA damage and G2 cell cycle arrest abrogation.

ABSTRACT: Ataxia telangiectasia and Rad3-related protein (ATR) is a key DNA damage response protein that facilitates DNA damage repair and regulates cell cycle progression. As such, ATR is an important component of the cellular response to radiation, particularly in cancer cells, which show altered DNA damage response and aberrant cell cycle checkpoints. Therefore, ATR's pharmacological inhibition could be an effective radiosensitization strategy to improve radiotherapy. We assessed the ability of an ATR inhibitor, AZD6738, to sensitize cancer cell lines of various histologic types to photon and proton radiotherapy. We found that radiosensitization took place through persistent DNA damage and abrogated G2 cell cycle arrest. We also found that AZD6738 increased the number of micronuclei after exposur

SUBMITTER: Bright SJ 

PROVIDER: S-EPMC11466186 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature