Towards a Structural Mechanism for Sister Chromatid Cohesion Establishment at the Eukaryotic Replication Fork.

Sarah S Henrikus,Alessandro Costa

doi:10.3390/biology10060466

Sarah S Henrikus, Alessandro Costa

Open Access

https://doi.org/10.3390/biology10060466

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Journal: Biology	Publication Date: May 26, 2021
Citations: 1	License type: CC BY 4.0

Affiliation: The Francis Crick Institute

Abstract

Cohesion between replicated chromosomes is essential for chromatin dynamics and equal segregation of duplicated genetic material. In the G1 phase, the ring-shaped cohesin complex is loaded onto duplex DNA, enriching at replication start sites, or "origins". During the same phase of the cell cycle, and also at the origin sites, two MCM helicases are loaded as symmetric double hexamers around duplex DNA. During the S phase, and through the action of replication factors, cohesin switches from encircling one parental duplex DNA to topologically enclosing the two duplicated DNA filaments, which are known as sister chromatids. Despite its vital importance, the structural mechanism leading to sister chromatid cohesion establishment at the replication fork is mostly elusive. Here we review the current understanding of the molecular interactions between the replication machinery and cohesin, which support sister chromatid cohesion establishment and cohesin function. In particular, we discuss how cryo-EM is shedding light on the mechanisms of DNA replication and cohesin loading processes. We further expound how frontier cryo-EM approaches, combined with biochemistry and single-molecule fluorescence assays, can lead to understanding the molecular basis of sister chromatid cohesion establishment at the replication fork.

Highlights

DNA replication and repair produce an accurate copy of the genome
The positively charged hinge lumen is critical for both nontopological and topological DNA association [19]. While it is debated whether a hinge gate is operated during cohesin loading onto duplex DNA [16,19,20,21], it is widely accepted that the loader complex named Scc2Mis4/Scc4Ssl3 plays a key role in this process by modulating both the Scc1–kleisin and the ATPase gates [22,23,24,25,26]
Crystallographic, cryo-EM, and single-molecule fluorescence studies led to the description of the architecture and dynamics of cohesin, informing its function

Summary

Introduction

DNA replication and repair produce an accurate copy of the genome. Equal segregation of duplicated chromosomes ensures that each daughter cell inherits one single copy of the genomic content. The loading factor Cdt1 renders MCM competent for origin recruitment by stabilising an open DNA gate in the helicase ring [2,3,6,7].

Results

Conclusion