Biology subjects

Poli, J.

Publications and source records attributed to Poli, J..

3 recordsLinked to original sources

bioRxiv2026

The replication checkpoint prevents fork stalling by reducing transcription

The replication checkpoint is essential for maintaining genome stability during replication stress. The prevailing view is that, without this pathway, stalled DNA replication forks lose structural integrity and collapse, preventing replication resumption and ultimately causing cell death. Here, we show that transcription is a major cause of replication stress in budding yeast checkpoint mutants. Checkpoint signaling limits replication defects by reducing RNA polymerase II and III occupancy at highly transcribed genes, particularly those encoding ribosomal proteins. Reducing transcription at these loci reduces fork stalling and the sensitivity of checkpoint mutants to hydroxyurea-induced replication stress. In human cells, transcription inhibition likewise improves replication recovery when ATR is inhibited, suggesting that this function is conserved. Together, our findings extend the canonical view of critical checkpoint functions: in addition to stabilizing stalled forks, it actively reduces RNA polymerase roadblocks that would otherwise impede their progression.

genetics↗

bioRxiv2026

The replication checkpoint couples fork progression to the release of transcribed genes from nuclear pores

The nuclear envelope contributes to chromatin compartmentalization in eukaryotes by anchoring heterochromatin to the lamina and active transcription sites to nuclear pore complexes (NPCs). During DNA replication, chromatin association with the nuclear envelope is thought to act as a topological barrier to DNA polymerases, potentially exacerbating transcription-replication conflicts (TRCs). While limited evidence suggests that the DNA replication checkpoint kinase Rad53/CHK1 promotes the release of genes from the NPC during replicative stress, the global scale and precise regulation of this process remain unknown. Through a candidate-based screen, we demonstrate that gene release from NPCs is a general feature of the cellular response to replication stress, tightly coordinated with replication fork progression. We show that the checkpoint kinases Mec1/ATR and Rad53/CHK1 are both essential for managing gene association with NPCs, but operate in a distinct, stepwise manner: Mec1/ATR triggers the initial dissociation by promoting the removal of RNAPII from the DNA, while Rad53/CHK1 prevents the premature reassociation of transcribed loci by phosphorylating the nucleoporin Mlp1. Finally, we demonstrate that maintaining this control over genes-NPC association is critical for efficient DNA replication under stress. Collectively, our findings reveal that the DNA replication checkpoint integrates genome duplication with chromosome spatial positioning to maintain genome integrity during replication stress.

genetics↗

bioRxiv2024

Genetic Foundations of Neurophysiological and Behavioural Variability Across the Lifespan

Neurophysiological brain activity shapes cognitive functions and individual traits. Here, we investigated the extent to which individual neurophysiological properties are genetically determined and how these adult traits align with cortical gene expression patterns across development. Using task-free magnetoencephalography in monozygotic and dizygotic twins, as well as unrelated individuals, we found that neurophysiological traits were significantly more similar between monozygotic twins, indicating a genetic influence, although individual-specific variability remained predominant. These heritable brain dynamics were predominantly associated with genes involved in neurotransmission, expressed along a topographical gradient that mirrors psychological functions, including attention, planning, and emotional processes. Furthermore, the cortical expression patterns of genes associated with individual differentiation aligned most strongly with gene expression profiles observed during adulthood in previously published longitudinal datasets. These findings underscore a persistent genetic influence on neurophysiological activity, supporting individual cognitive and behavioral variability.

neuroscience↗