Biology subjects

Zerjatke, T.

Publications and source records attributed to Zerjatke, T..

4 recordsLinked to original sources

bioRxiv2022

A ROS-dependent mechanism to drive progression through S phase

Long considered as cytotoxic reagents, reactive oxygen species (ROS) at the right concentration promote cell proliferation in cell culture, stem cells and model organisms. However, how ROS signaling is coordinated with cell cycle progression and integrated into the cell cycle control machinery on the molecular level remains unsolved. Here, we report oscillations of mitochondrial ROS during the cell cycle that target cyclin-dependent kinase 2 (CDK2). Chemical and metabolic interference with ROS production decrease T-loop phosphorylation on CDK2, impeding its full activation and thus efficient DNA replication. ROS regulate CDK2 activity through oxidation of a conserved cysteine residue in close proximity to the T-loop, which prevents binding of the T-loop phosphatase KAP. Together our data reveal how ROS couple mitochondrial metabolism to DNA replication and cell cycle progression, and provide a solution to the longstanding conundrum of how KAP activity towards CDKs can be cell cycle-regulated.

cell biology↗

bioRxiv2020

TraCurate: efficiently curating cell tracks

TraCurate is an open-source software tool to curate and manually annotate cell tracking data from time-lapse microscopy. Although many studies of cellular behavior require high-quality, long-term observations across generations of cells, automated cell tracking is often imperfect and typically yields fragmented results that still contain many errors. TraCurate provides the functionality for the curation and correction of cell tracking data with minimal user interaction and expenditure of time and supports the extraction of complete cell tracks and cellular genealogies from experimental data. Source code and binary packages for Linux, macOS and Windows are available at https://tracurate.gitlab.io/, as well as all other complementary tools described herein.

bioinformatics↗

bioRxiv2020

UFMylation regulates translational homeostasis and cell cycle progression

UFMylation, the posttranslational modification of proteins with ubiquitin fold modifier 1 (UFM1) is essential for metazoan life and is associated with multiple human diseases. Although UFMylation has been linked to endoplasmic reticulum (ER) stress, its biological functions and relevant cellular targets beyond the ER are obscure. Here, we show that UFMylation directly controls translation and cell division in a manner otherwise known for cellular homeostasis-sensing pathways such as mTOR. By combining cell cycle analyses, mass spectrometry and ribosome profiling we demonstrate that UFMylation is required for eIF4F translation initiation complex assembly and recruitment of the ribosome. Interference with UFMylation shuts down global translation, which is sensed by cyclin D1 and halts the cell cycle independently of integrated stress response signalling. Our findings establish UFMylation as a key regulator of translation and uncover a pathway that couples translational homeostasis to cell cycle progression via a ubiquitin-like modification.

cell biology↗

bioRxiv2019

Proliferative behavior of hematopoietic stem cells revisited: No evidence for mitotic memory

The proliferative activity of adult hematopoietic stem cells (HSCs) is controversially discussed. Inducible fluorescent histone 2B fusion protein (H2B-FP) transgenic mice are important tools for tracking the mitotic history of murine HSCs in label dilution experiments. A recent study proposed that the most primitive HSCs divide only four times, to then enter permanent quiescence. We observed that background fluorescence due to leaky H2B-FP expression, occurring in all H2B-FP transgenes independent of label induction, accumulated with age in primitive HSCs with high repopulation potential. We argue that this background had been misinterpreted as retention of induced label and permanent quiescence. We found cell division-independent half-lives of H2B-FPs to be short, which had led to overestimation of HSC divisional activity. Our data do not support HSC mitotic memory and entry into permanent quiescence after few divisions, but show that primitive HSCs of adult mice continue to cycle rarely.\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC=\"FIGDIR/small/745729v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (30K):\norg.highwire.dtl.DTLVardef@1b97626org.highwire.dtl.DTLVardef@fbc702org.highwire.dtl.DTLVardef@1c66b60org.highwire.dtl.DTLVardef@1b38f69_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗