Our Discoveries

Hoencamp et al., Science, 2021

Condensin II as a determinant of architecture type

In an incredible collaboration with the labs of Erez Lieberman Aiden, Jose Onuchic, Michele di Pierro, multiple NKI-based groups, and the DNA Zoo consortium, we study chromosome-scale genome folding across the eukaryotic tree of life. The absence of condensin II subunits turns out to correlate with the type of nuclear architecture. Depletion of condensin II in human cells transforms the folding of the human genome into a state as found in mosquitoes and fungi.

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Li et al., Nature, 2020

Genome folding by cohesin & CTCF

Cohesin folds the genome into loops that are anchored by CTCF. In a great collaboration with the lab of Daniel Panne, we show that the interaction of the CTCF N-terminus with the SA2-SCC1 subunits of cohesin stabilises cohesin at CTCF sites. This interaction is essential for CTCF-anchored loops genome-wide. We propose that CTCF enables chromatin loop formation by protecting cohesin against loop release.

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Elbatsh et al., Mol Cell, 2019

Condensin exhibits self-restraint

Chromosome condensation by condensin is essential for mitosis. In a wonderful collaboration with colleagues from Delft and Heidelberg, we find that one of condensin's ATPase sites promotes the initiation of loops, while the other site determines the type of loops that condensin forms. Mutation of this latter site yields hyper-active condensin that efficiently shortens chromosomes even in the total absence of condensin II.

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Haarhuis et al., Cell, 2017

Loop enlargement by cohesin

The cohesin complex shapes the 3D genome by looping together regulatory elements along chromosomes. We find that chromatin loop size can be increased, and that the duration with which cohesin embraces DNA determines the degree to which loops are enlarged. We conclude that the balanced activity of SCC2/NIPBL-dependent loop extension, and WAPL-mediated DNA release, allows cohesin to correctly structure chromosomes.

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Elbatsh et al., Mol Cell, 2016

How does cohesin release DNA?

Cohesin complexes by default undergo a continuous cycle of DNA entrapment and release. We uncover a functional asymmetry within the heart of cohesin's ABC-like ATPase machinery. Both ATPase sites contribute to DNA loading, whereas DNA release is controlled specifically by one site. We propose that Smc3 acetylation locks cohesin rings around sister DNAs by counteracting an activity associated with this release ATPase site.

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Haarhuis et al., Curr Biol, 2013

Why chromosomes are X-shaped

The classical X-shape of human chromosomes is the consequence of two distinct waves of cohesin removal. First cohesin is removed from arms, and only then from centromeres. We find that this two-step removal process allows the disentanglement of sister chromatids, and the correction of erroneous microtubule-kinetochore attachments. The two-step cohesin removal process thus is essential for proper chromosome segregation.

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Rowland et al., Mol Cell, 2009

Building sister chromatid cohesion

The co-entrapment of sister DNAs inside cohesin rings is dependent on the Eco1 acetyltransferase. We find that Eco1 triggers cohesion establishment by acetylating two key lysines in cohesin's Smc3 subunit. This acetylation counteracts an 'anti-establishment' activity associated with Wapl, and domains of Scc3 and Pds5. Smc3 acetylation turns out to stabilize cohesive cohesin by counteracting the opening of cohesin rings by Wapl.

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Sedeño Cacciatore, 2019

Turning heads and bending elbows

From the dynamic interphase genome to compacted mitotic chromosomes, DNA is organized by the SMC complexes cohesin and condensin. The picture emerges that these complexes structure the genome through a shared basic principle. We discuss the latest insights into how ATPase-driven conformational changes within these complexes may enlarge loops.

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van Ruiten, 2018

How do SMC complexes build loops?

What drives the formation of chromatin loops has been a long-standing question in chromosome biology. SMC complexes, conserved from bacteria to humans, turn out to be key to this process. These complexes structure chromosomes to enable mitosis and long-range gene regulation. Read our review on the wonderful world of SMC complexes.

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Haarhuis, 2014

The logic of X-shaped chromosomes

The X shape of chromosomes is one of the iconic images in biology. Cohesin in fact connects the sisters along their entire length until early mitosis. Then, cohesin's antagonist Wapl allows the separation of chromosome arms, resulting in the X shape of mitotic chromosomes. Check out our review on cohesin, its regulation, and the logic of X-shaped chromosomes.

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Our Discoveries

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