bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.03.05.641614

The NAT10 acetyltransferase modulates DNA damage-related factors and global 3D-genome architecture

Bartova, E.·Skalnikova, M.·Stixova, L.·Tichy, V.·Opaleny, F.·Byska, J.·Brom, T.·Legartova, S.
View original source ↗Export metadata ↓

Abstract

We explored the role of NAT10 acetyltransferase in the DNA damage response, focusing on its impact on 3D-genome architecture and DNA repair proteins. Compared to NAT10 wild-type (wt), NAT10 deficiency reduced XPC, DDB2, and p53 protein levels. In TP53 double-null (dn) cells, the NAT10 protein was undetectable, and DDB2 was significantly down-regulated. Although NAT10 depletion caused DDB2 down-regulation, it did not affect the DNA repair functions of the DDB2 protein. To this fact, protein interaction analysis revealed that UVC exposure weakens the DDB2-p53 interaction while strengthening the bond between NAT10 and DDB2. Also, AlphaFold 3 prediction tools showed a more potent interaction between DDB2 and p53 than DDB2 and NAT10 proteins implying that NAT10 rather regulates the DDB2-p53 protein complex. These proteomic NAT10-dependent changes coincided with alterations in chromatin interactions, particularly in acrocentric chromosomes, studied by the Hi-C technique. However, 3D-genome rearrangement, caused by NAT10 deficiency and UVC irradiation, did not significantly impact post-translational histone modifications. Overall, NAT10 depletion alters the pool of key DNA repair proteins and induces substantial 3D-genome reorganization. Graphical abstractThe effect of the NAT10 acetyltransferase depletion and UVC irradiation on 3D-genome nuclear architecture, histone signature, and the pool of selected DNA repair-related proteins. The figure was made using some icons adapted from BioRender software.

Explore related subjects

cell biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Bartova, E., Skalnikova, M., Stixova, L., Tichy, V., Opaleny, F., Byska, J., Brom, T., Legartova, S.. 2025-03-11. The NAT10 acetyltransferase modulates DNA damage-related factors and global 3D-genome architecture. https://doi.org/10.1101/2025.03.05.641614

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

OPN3 mediates retinal-dependent lipofuscin accumulation and its loss sensitizes keratinocytes to blue-light-induced proteomic remodeling

Lipofuscin is a blue-light-absorbing pigment that contributes to oxidative damage. Whether all-trans retinal (atRAL) contributes to its formation in response to light remains unclear. We asked whether blue-light photosensitization of atRAL promotes lipofuscin accumulation in human keratinocytes and whether this depends on Opsin 3 (OPN3). Blue-light excitation of atRAL reduced mitochondrial and lysosomal viability, impaired autophagic flux, and increased lipofuscin. OPN3 knockdown significantly reduced this accumulation. Label-free data-independent acquisition (DIA) proteomics showed that OPN3 acts at three levels. In the dark, OPN3 loss altered proteome networks associated with autophagy, apoptosis, and interferon-related responses. Under blue light, control cells activated a stress-adaptive program spanning inflammatory regulation, lipid metabolism, and mitochondrial function, which atRAL strongly amplified. This molecular signature, including induction of cellular respiration and ATP-production proteins, was largely absent when OPN3 was silenced. Respirometry showed that blue light suppressed oxygen consumption in both lines over the first 24 h, but a faster recovery in OPN3 knockdown cells at 48 and 72 h was observed. Together, these data define three functions of OPN3: maintaining the basal proteome in a blue-light-independent manner, enabling the adaptive blue-light response, and enabling retinal-dependent lipofuscin formation in keratinocytes.

cell biology↗
bioRxiv2026

Uncoupling microtubule lifetime, stability and post-translational modifications.

Microtubules (MTs) undergo continuous cycles of growth and disassembly. Because the transitions between these states are stochastic, MT age varies widely within a population. As MTs age, they are thought to accumulate post-translational modifications (PTMs) that, directly or indirectly, enhance their stability and thereby extend their lifetime. The rare MTs that withstand prolonged exposure to destabilizing drugs such as nocodazole (NZ) are indeed enriched in PTMs; yet the relationships between MT age, PTMs and stability remain unclear. Using microinjection of labelled tubulin, we measured microtubule network turnover in immortalized mouse embryonic fibroblasts. Half of the network was renewed within 3 minutes and 80% within 10 minutes, while approximately 5% of microtubules persisted for more than 20 minutes. These dynamics were comparable in quiescent and senescent cells, although the fraction of slowly renewing or non-renewing microtubules rose to 20% in senescent cells. Unexpectedly, neither the amount of PTMs (acetylation and detyrosination) nor resistance to NZ increased with MT age, and resistance to NZ was independent of these PTMs. Degrees of acetylation and detyrosination should therefore not be taken as readouts of MT age or stability. Because these PTMs do not accumulate on MTs over time, the chemical modification of polymerized tubulin is likely more reversible and dynamic than previously assumed.

cell biology↗
bioRxiv2026

Evidence of complete myofibril remodeling after severe damage in adult Drosophila.

Muscle function depends on the ability of myofibrils to withstand and repair mechanical damage, yet how adult muscles remodel damaged myofibrils remains poorly understood. Here, we establish a Drosophila model that allows the induction and longitudinal visualization of extensive myofibril damage and recovery in intact adult femur muscles. Sustained muscle depolarization caused extensive disruption of myofibrillar organization, with severe damage characterized by near-complete loss of Z-disc structures. Remarkably, myofibril architecture and muscle function were largely restored within days, revealing a substantial capacity for myofibril reconstruction in adult femur muscles. We identified two distinct states of myofibril damage, mild and severe, with mild damage appearing before severe damage during aging, suggesting a progressive process of myofibril deterioration and repair failure. We further show that filamins mechanosignaling is required for efficient myofibril remodeling. Following damage, wild-type filamin redistributes from the Z-disc and accumulates outside the myofibrils, whereas constitutively open filamin remains Z-disc-associated and constitutively closed filamin redistributes but results in increased damage and impaired recovery. These findings suggest that effective repair requires dynamic transitions between filamin conformational states and that filamin redistribution is an active component of the damage response rather than simply a consequence of muscle injury. During aging, filamin progressively redistributes from the Z-disc and muscle damage accumulates, with severe damage increasing after the appearance of mild damage. Together, our findings reveal a previously unappreciated capacity of adult muscle to reassemble damaged myofibrils and identify filamin mechanosignaling as a key component of this repair process, providing a framework for understanding how defective mechanosensing may contribute to age-related muscle decline and muscle disease.

cell biology↗