René H. Medema

Gene context shapes spatial organization and transcriptional heterogeneity of extrachromosomal DNA in cancer cells

This study investigates how gene context influences the spatial organization and transcriptional behavior of extrachromosomal DNA in cancer cells using a new imaging method called FLAGx.

Visualizing homology search in living cells

This study visualizes homology search dynamics in living human cells using GFP-MND1, revealing filament structures that resolve over time and depend on RAD54L and cohesin.

Transcription controls chromatin-nuclear lamina contacts through distinct Lamin A and LBR tethering mechanisms

This study shows that transcription inhibition rapidly and reversibly rewires chromatin-nuclear lamina contacts through distinct Lamin A and LBR tethering mechanisms.

The SKA complex is a mitotic vulnerability of chromosomally unstable cancers

The paper identifies the SKA complex as a mitotic vulnerability in chromosomally unstable cancers, showing its selective impact on these cells through prolonged mitosis.

Coordinated control of genome-nuclear lamina interactions by Topoisomerase 2B and Lamin B receptor

The paper identifies TOP2B as a regulator of genome-nuclear lamina interactions, showing its role in partitioning genomic regions between the nuclear lamina and interior, with LBR playing a complementary role.

Megabase-scale detachment of genome-nuclear lamina interactions is required for efficient repair of double stranded breaks

The paper shows that DSBs in LADs cause megabase-scale detachment from the nuclear lamina, which is necessary for efficient repair.

Extrachromosomal DNA micronucleation constrains tumour fitness andimproves patient survival

This study shows that ecDNA mis-segregation leads to micronuclei formation, reduced oncogene transcription, and improved patient survival in neuroblastoma.

Identification of critical factors of the replication stress response in human cells

The paper identifies genes critical for the replication stress response in human cells, revealing both known and novel factors that protect against replication stress-induced toxicity.

Widespread chromatin context-dependencies ofDNA double-strand break repair proteins

A multiplexed screen reveals how dozens of proteins sense the local chromatin context to tune the balance between two DNA repair pathways.

Chromatin context-dependent effects of epigenetic drugs on CRISPR-Cas9 editing

This study identifies 67 epigenetic drugs that modulate CRISPR-Cas9 editing efficiency and repair outcomes based on chromatin context in human cells.

Perturbations in 3D genome organization can promote acquired drug resistance

The paper shows that disrupting nuclear lamina association promotes ABCB1 gene derepression and taxol resistance in RPE cells.

Unexpected gene activation following CRISPR-Cas9-mediated genome editing

This study reports that lentiviral-based CRISPR-Cas9 vectors can integrate into the target genomic location, unexpectedly activating the target gene.

Performance of large scale pooled CRISPR screens is dependent on Cas9 expression levels

This study shows that Cas9 expression levels significantly affect the efficiency and speed of large-scale pooled CRISPR screens, with higher Cas9 expression improving performance.

Impact of chromatin context on Cas9-induced DNA double-strand break repair pathway balance

The paper measures how chromatin context influences the balance between DNA repair pathways after Cas9-induced breaks in over 1,000 genomic locations.

A FOXO-dependent replication checkpoint restricts proliferation of damaged cells

The paper identifies a FOXO-dependent mechanism that restricts proliferation of cells with mild replication stress by promoting premature activation of APC/CCDH1.

Condensin’s ATPase Machinery Drives and Dampens Mitotic Chromosome Condensation

This study shows that condensin complexes use opposing ATPase sites to drive and dampen chromosome condensation, with condensin II playing a key role in decatenation and axis formation.