Checkpoint kinase 1 (CHK1) and Cell cycle checkpoint protein RAD17 (RAD17) mRNAs (CHK1/RAD17 mRNA)

CHK1/RAD17 mRNA refers to the messenger RNA transcripts of Checkpoint kinase 1 (CHEK1) and Cell cycle checkpoint protein RAD17, which are pivotal nodes in the ATR-mediated DNA damage response (DDR) pathway [4, 7]. RAD17 facilitates the loading of the 9-1-1 complex onto damaged DNA, while CHK1 serves as the downstream kinase responsible for enforcing S and G2/M phase cell cycle checkpoints [7, 10]. Therapeutic targeting of these mRNAs, primarily through RNA interference (RNAi) or antisense oligonucleotides, aims to disrupt the DDR, thereby sensitizing cancer cells to genotoxic chemotherapy or radiotherapy [2, 6]. This strategy is especially relevant in p53-mutant cancers, which rely heavily on the G2/M checkpoint for DNA repair; its abrogation leads to mitotic catastrophe and cell death [3, 5]. Experimental constructs, such as siRNA-gemcitabine conjugates, have demonstrated synergistic efficacy in preclinical models of pancreatic and breast cancer by simultaneously delivering a cytotoxic agent and silencing these protective checkpoint genes [2, 9].

Other names

CHEK1 mRNARAD17 mRNAATR-CHK1 pathway mRNAsCheckpoint kinase 1 mRNACell cycle checkpoint protein RAD17 mRNA

The primary mechanism involves RNA interference (RNAi) mediated degradation of CHK1 and RAD17 mRNAs, leading to the depletion of their respective proteins and subsequent abrogation of the ATR-dependent DNA damage checkpoint.