Biology subjects

Johansen, J. V.

Publications and source records attributed to Johansen, J. V..

3 recordsLinked to original sources

bioRxiv2026

Dynamic interaction between tentacle-tethered microdomains in Integrator and NELF regulates the promoter-proximal pause checkpoint

Negative Elongation Factor (NELF) and Integrator are general regulators of transcriptional pausing and premature termination at the beginning of protein-coding genes. While NELF is a key pausing factor, Integrator triggers premature termination of dysfunctional RNAPII complexes. Here, we identify a direct interaction between the plant homeodomain (PHD) finger of Integrator subunit 12 (INTS12) and a previously unrecognized C-terminal domain (CTD) in the flexible tentacle of NELF-A. Mutation of either domain disrupts the interaction, and although RNAPII-associated pausing complexes still form, they are dysfunctional. Importantly, while deletion of the INTS12 PHD finger functionally mimics Integrator loss, a single point mutation in NELF-A CTD instead mimics loss of NELF, suggesting the presence of competitive interactions. Together, our findings uncover a novel mode of PHD finger binding and outline how an interaction between Integrator and NELF regulates transcriptional pausing and premature termination.

cell biology↗

bioRxiv2019

Mutations in a single signaling pathway allow growth on a different solvent than water

Since life is completely dependent on water, it is difficult to gauge the impact of solvent change. To analyze the role of water as a solvent in biology, we replaced water with heavy water (D2O), and investigated the biological effects by a wide range of techniques, using the fission yeast Schizosaccharomyces pombe as model organism. We show that high concentrations of D2O lead to altered glucose metabolism, growth retardation, and inhibition of meiosis. However, mitosis and overall cell viability were only slightly affected. After prolonged incubation in D2O, cells displayed gross morphological changes, thickened cell walls as well as aberrant septa and cytoskeletal organization. RNA sequencing revealed that D2O causes a strong downregulation of most tRNAs and triggers activation of the general stress response pathway. Genetic screens identified several D2O sensitive mutants, while mutants compromised in the cell integrity pathway, including the protein kinase genes pmk1, mkh1, pek1 and pck2, that control cell wall biogenesis, were more tolerant to D2O. We speculate that D2O affects the phospholipid membrane or cell wall glycans causing an activation of the cell integrity pathway. In conclusion, the effects of solvent replacement are pleiotropic but the D2O-triggered activation of the cell integrity pathway and subsequent increased deposition of cell wall material and septation problems appear most critical for the cell growth defects.

genetics↗

bioRxiv2018

A histone H4K20 methylation-mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing

The decompaction and re-establishment of chromatin organization immediately after mitosis is essential for genome regulation. The mechanisms underlying chromatin structure control in daughter cells are not fully understood. Here, we show that a chromatin compaction threshold in cells exiting mitosis ensures genome integrity by limiting replication licensing in G1 phase. Upon mitotic exit, appropriate chromatin relaxation is safeguarded by SET8-dependent methylation of histone H4 on lysine 20. Thus, in the absence of either SET8 or the H4K20 residue, substantial genome-wide chromatin decompaction occurs which allows excessive loading of the Origin Recognition Complex (ORC) in the daughter cells. ORC overloading stimulates aberrant recruitment of the MCM2-7 complex that promotes single-stranded DNA formation and DNA damage. Restoring chromatin compaction restrains excess replication licensing and the loss of genome integrity. Our findings identify a cell cycle-specific mechanism whereby fine-tuned chromatin relaxation suppresses excessive detrimental replication licensing and maintains genome integrity at the cellular transition from mitosis to G1 phase.

molecular biology↗