Bennie Lemmens Group
The recipe for life is encoded in DNA, a complex chain-like molecule built from four different types of nucleotides: A, T, C or G. The correct order of the three billion A’s, T’s, C’s and G’s of the human genome is critical, as a single mistake can be lethal or cause serious diseases such as cancer. We are interested in how human cells maintain, copy and propagate DNA.
Human life starts as a single cell that divides numerous times to create an entire human body consisting of trillions of cells. To maintain genome stability, cells need to faithfully replicate their DNA before dividing. A key feature of cancer cells is their forced proliferation, which causes a hasty uncontrolled start of DNA replication. To date, however, little is known about the mechanisms that control the start of DNA replication in human cells, hampering the design of better, selective cancer therapies. Studying essential, dynamic processes such as DNA replication requires conditional, time-resolved genetics. The Lemmens group develops and combines innovative protein depletion methods with cutting-edge imaging techniques to study how, when and where DNA replication starts. In parallel, we use various CRISPR-based technologies to discover new factors driving cell proliferation and cancer drug resistance.
We develop innovative approaches to study DNA replication with high precision in both time and space. To determine the mechanism and kinetics of human DNA replication we run various projects, ranging from targeted imaging approaches to unbiased genetic screens.
We currently focus on three projects:
- To study dynamic processes in human cells at single-cell resolution, our team develops rapid protein depletion methods and time-resolved analysis pipelines.
- To define where these processes take place in the cell, we develop cutting-edge imaging approaches, including live-cell, high-content, super resolution and/or expansion microscopy.
- Many of our projects involve CRISPR technologies, including gene knockouts, reporter knock-ins and gene editing approaches. We also use pooled CRISPR screens to study how human cells become resistant to cancer drugs and discover new factors controlling genome maintenance or DNA replication.
Interested in joining our team? Please feel free to email Bennie Lemmens.
DNA replication and mitotic entry: A brake model for cell cycle progression.
Lemmens B, Lindqvist A
J Cell Biol 2019 12;218(12):3892-3902
DNA Replication Determines Timing of Mitosis by Restricting CDK1 and PLK1 Activation.
Lemmens B, Hegarat N, Akopyan K, Sala-Gaston J, Bartek J, Hochegger H, Lindqvist A
Mol Cell 2018 07;71(1):117-128.e3
CRISPR/Cas9-targeted mutagenesis in Caenorhabditis elegans.
Waaijers S, Portegijs V, Kerver J, Lemmens BB, Tijsterman M, van den Heuvel S, Boxem M
Genetics 2013 Nov;195(3):1187-91
DNA double-strand break repair in Caenorhabditis elegans.
Lemmens BB, Tijsterman M
Chromosoma 2011 Feb;120(1):1-21
Mutagenic consequences of a single G-quadruplex demonstrate mitotic inheritance of DNA replication fork barriers.
Lemmens B, van Schendel R, Tijsterman M
Nat Commun 2015 Nov;6():8909
COM-1 promotes homologous recombination during Caenorhabditis elegans meiosis by antagonizing Ku-mediated non-homologous end joining.
Lemmens BB, Johnson NM, Tijsterman M
PLoS Genet 2013 ;9(2):e1003276
A role for the malignant brain tumour (MBT) domain protein LIN-61 in DNA double-strand break repair by homologous recombination.
Johnson NM, Lemmens BB, Tijsterman M
PLoS Genet 2013 ;9(3):e1003339
Polo-like kinase-1 controls proteasome-dependent degradation of Claspin during checkpoint recovery.
Mamely I, van Vugt MA, Smits VA, Semple JI, Lemmens B, Perrakis A, Medema RH, Freire R
Curr Biol 2006 Oct;16(19):1950-5
|Bennie Lemmens||Assistant professor|
|Gábor Merényi||Research assistant|
|Ann-Sofie Nilsson||Biomedical scientist|
|Abid Sayyid||Master student|
Understanding human biology and finding innovative cancer cures is a global team effort. We thus aim to collaborate with scientists around the world and currently join forces with i.a.:
- Dr. Thanos Halazonetis (University of Geneva, Switzerland)
- Dr. Hans Blom (Advanced Light microscopy Facility; KTH, Sweden)
- Dr. Mirek Dundr (Rosalind Franklin University, USA)
- Dr. Alexander van Oudenaarden (Hubrecht Institute, Netherlands)
- Dr. Bernard Schmierer (Genome Engineering Facility; KI, Sweden)
- Dr. Jiri Bartek (KI and Danish Cancer Society; Sweden and Denmark)
We are grateful for support from:
- Swedish Research Council (VR)
- Cancer Research KI
- Swedish Cancer Foundation
- Jeanssons foundation
- Karolinska Institutet faculty support
- Åke Wiberg foundation
Alfa building, floor 4