Biology subjects

Hume, S.

Publications and source records attributed to Hume, S..

3 recordsLinked to original sources

bioRxiv2026

Evolutionary Recoding of Olfactory Sensory Neurons

Odorant receptors (Ors) are the interface between an animals nervous system and its olfactory environment. In insect genomes, the Ors are often the largest gene family, and their rapid duplications and deletions result in extensive copy-number differences between species. Because olfactory sensory neurons (OSNs) typically express only one Or (the so-called one-receptor one-neuron rule), this dynamism at the level of Or genes raises fundamental questions regarding their cellular regulation: How do new Or duplicates gain their own neuron-specific expression? Such Or-OSN changes are thought to provide a key evolutionary path for modifying olfactory perception and related behaviours, but the absence of examples of these transitions has prevented an understanding of how they occur. Using a highly duplicated Drosophila Or subfamily (the Or67a subfamily) as a model system, we discovered parallel instances of Or67a duplicates gaining new OSN expression and reconstructed their evolutionary histories. Functional work in D. suzukii, a species with two novel Or67a-expressing OSN populations, revealed that their Or67a expression has arisen in preexisting OSNs, which have lost their ancestral Ors. As a result, these neurons were recoded and acquired new olfactory identities, thereby demonstrating the diversification of an OSN repertoire without the invention of developmentally new OSN lineages.

evolutionary biology↗

bioRxiv2021

The NUCKS1-SKP2-p21/p27 axis controls S phase entry

Efficient entry into S phase of the cell cycle is necessary for embryonic development and tissue homeostasis. However, unscheduled S phase entry triggers DNA damage and promotes oncogenesis, underlining the requirement for strict control. Here, we identify the NUCKS1-SKP2-p21/p27 axis as a checkpoint pathway for the G1/S transition. In response to mitogenic stimulation, NUCKS1, a transcription factor, is recruited to chromatin to activate expression of SKP2, the F-box component of the SCFSKP2 ubiquitin ligase, leading to degradation of p21 and p27 and promoting progression into S phase. In contrast, DNA damage induces p53-dependent transcriptional repression of NUCKS1, leading to SKP2 downregulation, p21/p27 upregulation, and cell cycle arrest. We propose that the NUCKS1-SKP2-p21/p27 axis integrates mitogenic and DNA damage signalling to control S phase entry. TCGA data reveal that this mechanism is hijacked in many cancers, potentially allowing cancer cells to sustain uncontrolled proliferation.

cancer biology↗

bioRxiv2019

Cyclin F-Chk1 synthetic lethality mediated by E2F1 degradation

Cyclins are central engines of cell cycle progression when partnered with Cyclin Dependent Kinases (CDKs). Among the different cyclins controlling cell cycle progression, cyclin F does not partner with a CDK, but forms an E3 ubiquitin ligase, assembling through the F-box domain, an Skp1-Cul1-F-box (SCF) module. Although multiple substrates of cyclin F have been identified the vulnerabilities of cells lacking cyclin F are not known. Thus, we assessed viability of cells lacking cyclin F upon challenging cells with more than 200 kinase inhibitors. The screen revealed a striking synthetic lethality between Chk1 inhibition and cyclin F loss. Chk1 inhibition in cells lacking cyclin F leads to DNA replication catastrophe. The DNA replication catastrophe depends on the accumulation of E2F1 in cyclin F depleted cells. We observe that SCFcyclin F promotes E2F1 degradation after Chk1 inhibitors in a CDK dependent manner. Thus, Cyclin F restricts E2F1 activity during cell cycle and upon checkpoint inhibition to prevent DNA replication stress. Our findings pave the way for patient selection in the clinical use of checkpoint inhibitors.

cancer biology↗