MCM2-7-dependent cohesin loading during S phase promotes sister-chromatid cohesion
Abstract
DNA replication transforms cohesin rings dynamically associated with chromatin into the cohesive form to establish sister-chromatid cohesion. Here, we show that, in human cells, cohesin loading onto chromosomes during early S phase requires the replicative helicase MCM2-7 and the kinase DDK. Cohesin and its loader SCC2/4 (NIPBL/MAU2 in humans) associate with DDK and phosphorylated MCM2-7. This binding does not require MCM2-7 activation by CDC45 and GINS, but its persistence on activated MCM2-7 requires fork-stabilizing replisome components. Inactivation of these replisome components impairs cohesin loading and causes interphase cohesion defects. Interfering with Okazaki fragment processing and nucleosome assembly does not impact cohesion. Therefore, MCM2-7-coupled cohesin loading promotes cohesion establishment, which occurs without Okazaki fragment maturation. We propose that the cohesin-loader complex bound to MCM2-7 is mobilized upon helicase activation, transiently held by the replisome, and deposited behind the replication fork to encircle sister chromatids and establish cohesion.
Data availability
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MCM2-7-dependent cohesin loading during S phase promotes sister-chromatid cohesionPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE112018).
Article and author information
Author details
Funding
Howard Hughes Medical Institute
- Hongtao Yu
Welch Foundation
- Hongtao Yu
Cancer Prevention and Research Institute of Texas
- Hongtao Yu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Antoine M van Oijen, University of Wollongong, Australia
Version history
- Received: November 28, 2017
- Accepted: March 31, 2018
- Accepted Manuscript published: April 3, 2018 (version 1)
- Version of Record published: April 12, 2018 (version 2)
Copyright
© 2018, Zheng et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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