NIPBL and cohesin: new take on a classic tale

Dácil Alonso-Gil; Ana Losada

doi:10.1016/j.tcb.2023.03.006

NIPBL and cohesin: new take on a classic tale

Trends Cell Biol. 2023 Oct;33(10):860-871. doi: 10.1016/j.tcb.2023.03.006. Epub 2023 Apr 15.

Authors

Dácil Alonso-Gil¹, Ana Losada²

Affiliations

¹ Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
² Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. Electronic address: alosada@cnio.es.

PMID: 37062615
DOI: 10.1016/j.tcb.2023.03.006

Abstract

Cohesin folds the genome in dynamic chromatin loops and holds the sister chromatids together. NIPBL^Scc2 is currently considered the cohesin loader, a role that may need reevaluation. NIPBL activates the cohesin ATPase, which is required for topological entrapment of sister DNAs and to fuel DNA loop extrusion, but is not required for chromatin association. Mechanistic dissection of these processes suggests that both NIPBL and the cohesin STAG subunit bind DNA. NIPBL also regulates conformational switches of the complex. Interactions of NIPBL with chromatin factors, including remodelers, replication proteins, and the transcriptional machinery, affect cohesin loading and distribution. Here, we discuss recent research addressing how NIPBL modulates cohesin activities and how its mutation causes a developmental disorder, Cornelia de Lange Syndrome (CdLS).

Keywords: 3D genome; CTCF; Cornelia de Lange Syndrome; STAG1; STAG2; loop extrusion.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Cell Cycle Proteins* / genetics
Cell Cycle Proteins* / metabolism
Chromatin
Chromosomal Proteins, Non-Histone* / genetics
Chromosomal Proteins, Non-Histone* / metabolism
Cohesins
Humans

Substances

Cell Cycle Proteins
Chromosomal Proteins, Non-Histone
Chromatin
NIPBL protein, human