Human CST suppresses origin licensing and promotes AND-1/Ctf4 chromatin association.
| Autor: | Wang Y; Department of Biological Sciences, University of South Carolina, Columbia, SC, USA., Brady KS; Department of Biological Sciences, University of South Carolina, Columbia, SC, USA., Caiello BP; Department of Biological Sciences, University of South Carolina, Columbia, SC, USA., Ackerson SM; Department of Biological Sciences, University of South Carolina, Columbia, SC, USA., Stewart JA; Department of Biological Sciences, University of South Carolina, Columbia, SC, USA jason.stewart@sc.edu.; Center for Colon Cancer Research, University of South Carolina, Columbia, SC, USA. |
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| Jazyk: | angličtina |
| Zdroj: | Life science alliance [Life Sci Alliance] 2019 Apr 12; Vol. 2 (2). Date of Electronic Publication: 2019 Apr 12 (Print Publication: 2019). |
| DOI: | 10.26508/lsa.201800270 |
| Abstrakt: | 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. (© 2019 Wang et al.) |
| Databáze: | MEDLINE |
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