TY - JOUR T1 - Human CST suppresses origin licensing and promotes AND-1/Ctf4 chromatin association JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201800270 VL - 2 IS - 2 SP - e201800270 AU - Yilin Wang AU - Kathryn S Brady AU - Benjamin P Caiello AU - Stephanie M Ackerson AU - Jason A Stewart Y1 - 2019/04/01 UR - https://www.life-science-alliance.org/content/2/2/e201800270.abstract N2 - Human CTC1-STN1-TEN1 (CST) is an RPA-like single-stranded DNA-binding protein that interacts with DNA polymerase α-primase (pol α) and functions in telomere replication. Previous studies suggest that CST also promotes replication restart after fork stalling. However, the precise role of CST in genome-wide replication remains unclear. In this study, we sought to understand whether CST alters origin licensing and activation. Replication origins are licensed by loading of the minichromosome maintenance 2–7 (MCM) complex in G1 followed by replisome assembly and origin firing in S-phase. We find that CST directly interacts with the MCM complex and disrupts binding of CDT1 to MCM, leading to decreased origin licensing. We also show that CST enhances replisome assembly by promoting AND-1/pol α chromatin association. Moreover, these interactions are not dependent on exogenous replication stress, suggesting that CST acts as a specialized replication factor during normal replication. Overall, our findings implicate CST as a novel regulator of origin licensing and replisome assembly/fork progression through interactions with MCM, AND-1, and pol α. ER -