New research from a team of genome scientists and DNA damage response experts breaks new ground in understanding the function of a protein currently limited in clinical trials for cancer treatments. Led by Haichao Zhao, PhD, in the Yan Lab at UNC Charlotte, the new research shows how ATM-mediated signaling is induced by DNA single-strand breaks (SSBs) for DNA damage repair – illuminating the distinct mechanisms of SSB-induced ATM kinase and shedding an important light on APE1 function. In the new study, published today in Nature Communications , researchers demonstrate their use of plasmid-based SSB structures to examine APE1's critical role in DNA damage response (DDR) signaling pathways.
Among other findings, the publication details results showing SSB induces ATM activation prior to ATR, temporarily arresting cell cycle progression as DNA attempts to undergo repair. And – central to the study's significance – the team discovere direct evidence for the active role played by APE1, a multifunctional enzyme, in SSB-induced ATM DDR signaling. "We demonstrate that APE1 promotes SSB-induced ATM DDR through at least two mechanisms: APE1 exonuclease activity-mediated SSB processing and APE1-mediated direct recruitment of ATM to SSBs," researchers wrote.
Building upon the Yan Lab's prior work at UNC Charlotte, the findings are a strong step forward in our understanding of SSB DNA repair and cellular response – and may contribute to future therapeutic inhibitor options for a .