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Updated: Feb 12, 2026

Using Fluorescence In Situ Hybridization FISH to Monitor the State of Arm Cohesion in Prometaphase and Metaphase I Drosophila Oocytes
Published on: December 6, 2017
MCM2-7-dependent cohesin loading during S phase promotes sister-chromatid cohesion
Ge Zheng1, Mohammed Kanchwala2, Chao Xing2,3,4
1Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States.
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 or 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.
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