Judith Haarhuis

Associate Staff scientist

My interest lies in the molecular mechanism behind chromosomal architecture. DNA is structured via chromosomal loops created by cohesin. At the moment we are at the exciting point to understand where cohesin will create loops, how to maintain this and what the effect of these loops have on cellular behaviour.

Molecular Biology

Genetics

Cell Biology

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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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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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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Dev Cell, 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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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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Workexperience

2004-2008. – Bachelor of Science, University of Utrecht.
2008-2010 – Master of Science, University of Utrecht including an intership in the lab of Karlene Cimprich at Stanford University.
2010 – 2016 – PhD in Molecular Biology, Utrecht University, in the lab of Benjamin Rowland at The Netherlands Cancer Institute.

Judith Haarhuis

Associate Staff scientist

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