RT Journal Article
SR Electronic
T1 Human CST suppresses origin licensing and promotes AND-1/Ctf4 chromatin association
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 561977
DO 10.1101/561977
A1 Yilin Wang
A1 Kathryn S. Brady
A1 Benjamin Caiello
A1 Stephanie M. Ackerson
A1 Jason A. Stewart
YR 2019
UL http://biorxiv.org/content/early/2019/02/27/561977.abstract
AB 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 following 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.