bims-mirnam 2025-11-23 papers

bims-mirnam

Biomed News

on Mitochondrial RNA metabolism

Issue of 2025–11–23
thirteen papers selected by
Hana Antonicka, McGill University

Glutathionylated DNA adducts accumulate in mitochondrial DNA and are regulated by AP endonuclease 1 and tyrosyl-DNA phosphodiesterase 1.
Caloric restriction enhances inheritance of wild-type mitochondrial DNA in Saccharomyces cerevisiae.
Mitochondrial transplantation restores mitochondrial content and function in SSBP1-related mitochondrial DNA depletion syndrome.
Elucidating the Localization and Interactome of Mitochondrial Microproteins.
Substrate and enzyme determinants for recognition by human mitochondrial RNase P.
An inherited mitochondrial DNA mutation remodels inflammatory cytokine responses in macrophages and in vivo in mice.
Ribosome-induced mRNA pseudoknot interactions visualized by DMS MaP-Seq.
MTERF1 Regulates Podocyte Mitochondrial DNA Replication Impairment and Mitochondrial Dysfunction in Diabetic Nephropathy through the AMPK/mTOR Pathway.
Interplay between codon usage and ribosome heterogeneity: A new layer of translational regulation.
Knockdown of SUCLG2 inhibits glioblastoma proliferation and promotes apoptosis through LMNA acetylation and the mediation of H4K16la lactylation.
Plasmodium mitochondrial exodeoxyribonucleases, Exomit1 and Exomit2, are conserved within alveolates with Exomit1 essential for the establishment of blood-stage infection.
Mitochondrial Transfer Rescues Respiration to Support De Novo Pyrimidine Biosynthesis and Tumor Progression.
DNA G-quadruplexes: Structural and functional insights.

Proc Natl Acad Sci U S A. 2025 Nov 25. 122(47): e2509312122

Glutathionylated DNA adducts accumulate in mitochondrial DNA and are regulated by AP endonuclease 1 and tyrosyl-DNA phosphodiesterase 1.

Yu Hsuan Chen, Martin Esparza Sanchez, Ta I Hung, Jin Tang, Wenyan Xu, Jiekai Yin, Yinsheng Wang, Chia-En A Chang, Huimin Zhang, Junjie Chen, Linlin Zhao.

  Mitochondrial DNA (mtDNA) is crucial for cellular energy production, metabolism, and signaling. Its dysfunction is implicated in various diseases, including mitochondrial disorders, neurodegeneration, and diabetes. mtDNA is susceptible to damage by endogenous and environmental factors; however, unlike nuclear DNA (nDNA), mtDNA lesions do not necessarily lead to an increased mutation load in mtDNA. Instead, mtDNA lesions have been implicated in innate immunity and inflammation. Here, we report a type of mtDNA damage: glutathionylated DNA (GSH-DNA) adducts. These adducts are formed from abasic (AP) sites, key intermediates in base excision repair, or from alkylation DNA damage. Using mass spectrometry, we quantified the GSH-DNA lesion in both nDNA and mtDNA and found its significant accumulation in mtDNA of two different human cell lines, with levels one or two orders of magnitude higher than in nDNA. The formation of GSH-DNA adducts is influenced by TFAM and polyamines, and their levels are regulated by repair enzymes AP endonuclease 1 (APE1) and tyrosyl-DNA phosphodiesterase 1 (TDP1). The accumulation of GSH-DNA adducts is associated with the downregulation of several ribosomal and complex I subunit proteins and the upregulation of proteins related to redox balance and mitochondrial dynamics. Molecular dynamics (MD) simulations revealed that the GSH-DNA lesion stabilizes the TFAM-DNA binding, suggesting shielding effects from mtDNA transactions. Collectively, this study provides critical insights into the formation, regulation, and biological effects of GSH-DNA adducts in mtDNA. Our findings underscore the importance of understanding how these lesions may contribute to innate immunity and inflammation.

Keywords:  DNA damage; DNA repair; GSH; PRDX6; TFAM

DOI:  https://doi.org/10.1073/pnas.2509312122
Sci Rep. 2025 Nov 17. 15(1): 40201

Caloric restriction enhances inheritance of wild-type mitochondrial DNA in Saccharomyces cerevisiae.

Wenjuan Zhu, Minoru Yoshida, Feng Ling.

  In Saccharomyces cerevisiae, an asymmetrical division model, mitochondrial (mt) DNA typically exists in a homoplasmic state, but mutations frequently occur. Rolling-circle replication, mediated by the mtDNA recombinase Mhr1p, forms tandem concatemers that are selectively transmitted to budding cells. In crosses between haploids with wild-type (ρ+) and hypersuppressive (HS) ρ- mtDNA, ρ- progeny are predominantly produced due to the replicative advantage of mtDNA with large deletions. We investigated the effects of caloric restriction (CR; 0.5% glucose medium) on mitochondrial distribution and found that ρ+ mtDNA-mitochondria are pre-selected in zygotes and transmitted into buds prior to mitochondrial fusion. This process, termed ρ+ mtDNA-mitochondrial preselection and transmission (ρ+ mtDNA-MPT), was validated by confocal imaging and flow cytometry analyses. The rate of ρ+ progeny increased under CR conditions compared to glucose-abundant media, suggesting that CR enhances ρ+ mtDNA-MPT and promotes the formation of wild-type mtDNA homoplasmy via an Mhr1p-dependent mechanism, which dominates mtDNA inheritance.

Keywords:  Heteroplasmy; Homoplasmy; Hypersuppresiveness; Mitochondria; Nonmedial budding.; Preselection; mtDNA

DOI:  https://doi.org/10.1038/s41598-025-23888-x
BMB Rep. 2025 Nov 20. pii: 6418. [Epub ahead of print]

Mitochondrial transplantation restores mitochondrial content and function in SSBP1-related mitochondrial DNA depletion syndrome.

Dohee Kim, Seo-Eun Lee, JuHyuen Cha, Jun Ho Lee, Young Cheol Kang, Sang-Yeon Lee.

This study examined therapeutic potential of mitochondrial transplantation using PN-101, a mitochondria preparation derived from human umbilical cord mesenchymal stem cells (UCMSCs), to address SSBP1-related mitochondrial DNA (mtDNA) depletion syndrome. Patient-derived fibroblasts harboring a heterozygous SSBP1 mutation (c.272G＞A:p.Arg91Gln) were treated with PN-101. Its successful uptake and integration into these cells were confirmed. Subsequent analyses revealed that PN-101 treatment significantly increased mtDNA copy numbers in a time- and dose-dependent manner, elevated the expression of key oxidative phosphorylation proteins, and enhanced overall mitochondrial bioenergetics. Taken together, these results provide strong evidence that mitochondrial transplantation holds promise as a therapeutic strategy for primary mitochondrial diseases, including those involving SSBP1 mutations.
Methods Mol Biol. 2026 ;2992 213-228

Elucidating the Localization and Interactome of Mitochondrial Microproteins.

Jiemin Nah, Pooja Sridharan, Lena Ho.

  A large number of novel microproteins discovered to date are nuclear encoded, mitochondrial proteins, pointing to their widespread roles in metabolic regulation. In this chapter, we provide a workflow of how to verify if a candidate microprotein is localized to the mitochondria, its submitochondrial localization (i.e., outer, inner membrane, or matrix) and how to determine its interactome in order to elucidate its molecular function.

Keywords:  Microproteins; Mitochondria; OXPHOS

DOI:  https://doi.org/10.1007/978-1-0716-5013-4_15
Nucleic Acids Res. 2025 Nov 13. pii: gkaf1145. [Epub ahead of print]53(21):

Substrate and enzyme determinants for recognition by human mitochondrial RNase P.

Enxhi Hazisllari, Danijela Radovanović, Ursula Toth, Elisa Vilardo, Roland K Hartmann, Walter Rossmanith.

RNase P enzymes of widely varying architectures recognize the 5'-leader/acceptor-stem junction and the D/T loop-interaction region of precursor tRNAs to direct cleavage to the 5' end of tRNAs. In contrast, human mitochondrial RNase P (mtRNase P) encases the entire tRNA with the aid of the methyltransferase subcomplex TRMT10C-SDR5C1. Here, we performed a kinetic analysis of substrate recognition by mtRNase P using substrate and protein variants. Surprisingly, processing by mtRNase P was found to be more efficient for tRNA precursors with longer 5' extensions and decreased sharply at a leader length of 1 nt. MtRNase P also employs a more rigid "measuring mechanism" for cleavage-site selection than the related single-subunit enzymes, so that even substrates with a G:C base-pair extension of the acceptor stem are cleaved predominantly at the canonical site. The specific contacts of TRMT10C-SDR5C1 with the anticodon loop are not crucial for efficient processing, but without interactions with the pre-tRNA, TRMT10C-SDR5C1 is unable to stimulate cleavage by the nuclease subunit PRORP, also explaining why mtRNase P reaches its limits with the D-armless mitochondrial tRNASer(AGY). Our findings set human mtRNase P apart in terms of substrate recognition from all other known forms of RNase P, including the related single-polypeptide PRORPs.

DOI: https://doi.org/10.1093/nar/gkaf1145
Nat Commun. 2025 Nov 20. 16(1): 10222

An inherited mitochondrial DNA mutation remodels inflammatory cytokine responses in macrophages and in vivo in mice.

Eloïse Marques, Stephen P Burr, Alva M Casey, Richard J Stopforth, Chak Shun Yu, Keira Turner, Dane M Wolf, Marisa Dilucca, Vincent Paupe, Suvagata Roy Chowdhury, Victoria J Tyrrell, Robbin Kramer, Yamini M Kanse, Chinmayi Pednekar, Chris A Powell, James B Stewart, Julien Prudent, Michael P Murphy, Michal Minczuk, Valerie B O'Donnell, Clare E Bryant, Patrick F Chinnery, Arthur Kaser, Alexander von Kriegsheim, Dylan G Ryan.

Impaired mitochondrial bioenergetics in macrophages promotes hyperinflammatory cytokine responses, but whether inherited mtDNA mutations drive similar phenotypes is unknown. Here, we profiled macrophages harbouring a heteroplasmic mitochondrial tRNAAla mutation (m.5019A>G) to address this question. These macrophages exhibit combined respiratory chain defects, reduced oxidative phosphorylation, disrupted cristae architecture, and compensatory metabolic adaptations in central carbon metabolism. Upon inflammatory activation, m.5019A>G macrophages produce elevated type I interferon (IFN), while exhibiting reduced pro-inflammatory cytokines and oxylipins. Mechanistically, suppression of pro-IL-1β and COX2 requires autocrine IFN-β signalling. IFN-β induction is biphasic: an early TLR4-IRF3 driven phase, and a later response involving mitochondrial nucleic acids and the cGAS-STING pathway. In vivo, lipopolysaccharide (LPS) challenge of m.5019A>G mice results in elevated type I IFN signalling and exacerbated sickness behaviour. These findings reveal that a pathogenic mtDNA mutation promotes an imbalanced innate immune response, which has potential implications for the progression of pathology in mtDNA disease patients.

DOI: https://doi.org/10.1038/s41467-025-65023-4
bioRxiv. 2025 Oct 01. pii: 2024.12.07.627321. [Epub ahead of print]

Ribosome-induced mRNA pseudoknot interactions visualized by DMS MaP-Seq.

Preston A Kellenberger, Zhenwei Song, Xiao Heng, Peter V Cornish.

Examining the dynamicity of RNA structure has deepened our understanding of its vast biological functions. Perhaps the protein complex that encounters the most diverse landscape of RNA structure is the ribosome. In translation, the ribosome must linearize countless mRNA conformations for proper protein production. Some RNA structures, however, reliably make up sequences which hinder the ability of the ribosome to maintain its reading frame. The most well-studied of these structures is the RNA pseudoknot. Here, we present an approach utilizing dimethyl sulfate probing with mutational profiling and sequencing (DMS MaP-Seq) to precisely examine RNA unwinding. We employ the method to understand the unfolding of the Sugarcane Yellow Leaf Virus pseudoknot (ScYLV PK ). Notably, we find that the helical junction is stabilized in the presence of the ribosome and is contingent upon hydrogen bonding at the 27 th residue of ScYLV PK . Additionally, it is demonstrated that the ribosome destabilizes wildtype ScYLV PK in a manner independent of A/P-site occupancy. Together, these results establish DMS MaP-Seq as a sensitive tool for detecting ribosome-induced RNA conformational changes and reveal specific structural motifs that govern pseudoknot stability during translation.

DOI: https://doi.org/10.1101/2024.12.07.627321
Ann Clin Lab Sci. 2025 Sep;55(5): 663-671

MTERF1 Regulates Podocyte Mitochondrial DNA Replication Impairment and Mitochondrial Dysfunction in Diabetic Nephropathy through the AMPK/mTOR Pathway.

Haiying Tao, Ling'an Yu.

OBJECTIVE: This study was carried out with an objective to clarify the mechanism of mitochondrial transcription termination factor 1 (MTERF1) in regulating mitochondrial DNA (mtDNA) replication and mitochondrial function of podocytes in diabetic nephropathy (DN).
METHODS: To establish a type I diabetes model, C57BL/6J mice were injected intraperitoneally with streptozotocin (STZ). Eight weeks after STZ injection, blood glucose levels and renal function were assessed in mice. Mouse renal tissues were analyzed via hematoxylin-eosin, periodic acid-Schiff, and TdT-mediated dUTP nick-end labeling staining. Immunohistochemistry/Western blot were employed for the detection of MTERF1 expression. MPC-5 cells were treated with high glucose (HG) (30 mM) to establish the cellular model. MTERF1-overexpressing MPC-5 cells were constructed and treated with HG and the AMP-activated protein kinase (AMPK) inhibitor compound C (CC) for 24 h. Cell apoptosis was assessed by flow cytometry, cell viability by the cell counting kit-8 assay, mtDNA copy number by real-time quantitative PCR, adenosine triphosphate (ATP) production by ultraviolet spectrophotometric method, mitochondrial reactive oxygen species (mtROS) by MitoSox, and mitochondrial membrane potential (MMP) by JC-1. MTERF1 protein expression and AMPK/mammalian target of rapamycin (mTOR) signaling pathway activity were measured via Western blot.
RESULTS: The model group (relative to the control group) exhibited a significant rise in blood glucose, urine volume, urinary albumin, and urine albumin-creatinine ratio, along with significantly aggravated glomerular injury and markedly increased glycogen deposition and decreased MTERF1 expression in mouse renal tissue. In in vitro experiments, compared with the normal glucose (NG) group, the HG group showed increased apoptosis and reduced cell activity, accompanied by significantly decreased MTERF1 protein expression, mtDNA copy number, and ATP content. Compared to the HG+oe-NC group, the HG+oe-MTERF1 group showed significant increases in mtDNA copy number, ATP content, MMP, and AMPK/mTOR signaling pathway activity, while demonstrating decreased mtROS production. The HG+oe-MTERF1+CC group exhibited significant reductions in mtDNA copy number, ATP production, and AMPK/mTOR signaling pathway activity compared to the HG+oe-MTERF1 group, but displayed elevated mtROS levels.
CONCLUSION: Over-expression of MTERF1 can alleviate HG-induced damage of mtDNA replication and mitochondrial dysfunction in podocytes via activating the AMPK/mTOR signaling pathway, thus improving DN.

Keywords: AMPK/mTOR signaling pathway; MTERF1; diabetic nephropathy; mitochondrial dysfunction
Biochem Biophys Res Commun. 2025 Nov 16. pii: S0006-291X(25)01687-0. [Epub ahead of print]792 152971

Interplay between codon usage and ribosome heterogeneity: A new layer of translational regulation.

Ujwal Dahal, Anu Bansal, Anshu Raj Dahal, Mukti Ram Aryal, Barsha Khanal.

  Codon usage bias (CUB) and ribosome heterogeneity represent two fundamental yet traditionally separate dimensions of translational regulation. CUB, defined as the preferential use of synonymous codons, influences translation efficiency, fidelity, mRNA stability, and protein folding. Ribosome heterogeneity, arising from variability in ribosomal RNA modifications, ribosomal protein composition, and tissue-specific paralogs, generates specialized ribosomes with selective mRNA translation capacity. Emerging evidence reveals that these two regulatory axes are functionally interconnected: specialized ribosomes preferentially translate transcripts enriched in distinct codon usage patterns, regulating protein synthesis during development, stress adaptation, and disease progression. This interplay reshapes the classical view of translation by integrating codon context with ribosome specialization, forming a "ribosome code" that governs proteome composition. Disruption of this axis contributes to diverse diseases, including cancer, ribosomopathies, and neurodevelopmental disorders, where codon-specific translational reprogramming drives pathogenic protein expression. Advances in ribosome profiling, cryo-EM, and integrative computational modeling have illuminated these dynamics at unprecedented resolution, offering new opportunities for targeted therapeutic interventions. This review synthesizes current knowledge on codon-ribosome interactions, explores their mechanistic basis and functional implications, and highlights future research directions toward decoding this emerging layer of translational control.

Keywords:  Codon usage bias; RNA modification; Ribosome heterogeneity; Specialized ribosomes; Translational regulation

DOI:  https://doi.org/10.1016/j.bbrc.2025.152971
Cell Death Discov. 2025 Nov 17. 11(1): 534

Knockdown of SUCLG2 inhibits glioblastoma proliferation and promotes apoptosis through LMNA acetylation and the mediation of H4K16la lactylation.

Wenshan Li, Qingqing Zhang, Hang Yin, Qiao Li, Shangyu Liu, Juncheng Wang, Guoqiang Yuan, Yawen Pan.

Glioblastoma (GBM) is the most aggressive primary tumour in the central nervous system, and dynamic clonal evolution and interactions within the microenvironment cause its significant spatiotemporal heterogeneity. These interactions primarily manifest as metabolic reprogramming, mitochondrial dynamic imbalance, and epigenetic remodelling. SUCLG2 has been implicated in the progression of GBM; however, the underlying mechanism is unclear. This study aimed to investigate the role of SUCLG2 in the proliferation and apoptosis of GBM cells. SUCLG2 was found to interact with LMNA, leading to acetylation modification of its amino acid residue K470 and affecting limited oxidative phosphorylation levels and mitochondrial damage. SUCLG2 interacted with DLAT, reducing the binding of lactate-regulated protein H4K16la to promoter regions and cis-regulatory elements. This suppressed the expression of BEST1, GRAMD4, and MBD6, affecting the proliferation and apoptosis of GBM cells. These findings reveal a new SUCLG2-mediated mechanism in lactate metabolism and mitochondrial apoptosis in GBM and offer novel therapeutic and preventive targets for GBM.

DOI: https://doi.org/10.1038/s41420-025-02856-4
FEBS J. 2025 Nov 16.

Plasmodium mitochondrial exodeoxyribonucleases, Exomit1 and Exomit2, are conserved within alveolates with Exomit1 essential for the establishment of blood-stage infection.

Shivani Mishra, Tribeni Chatterjee, Pragya Mehra, Abhilasha Gahlawat, Simmi Pradhan, Ritika Gupta, Mrinal Kanti Bhattacharyya, Satish Mishra, Saman Habib.

  The 6-kb linear repeat genome of the mitochondrion (mtDNA) of the malaria parasite is among the smallest known in nature, but is well-conserved in comparison with its apicoplast and nuclear genomes. Except for the presence of base excision repair (BER) and two double-strand break repair (DSBR) proteins in mitochondria, the mechanisms for preservation of mtDNA integrity during traversal of the parasite through different cell types and environments in the mosquito vector and mammalian host are not characterized. We identified two putative organellar exonucleases in Plasmodium falciparum, PfExomit1 and PfExomit2, with homologs present only within certain alveolates. Immunofluorescence localization and chromatin immunoprecipitation experiments using antibodies generated against recombinant proteins showed that they are localized to the mitochondrion. PfExomit1 and PfExomit2 demonstrated specificity for different DNA substrates; PfExomit1 cleaved ssDNA in both polarities, while PfExomit2 was a bipolar exonuclease on dsDNA with 3'-5' exonuclease activity on ssDNA. The mismatch repair (MMR) protein PfMutS, which carries an additional endonuclease domain, was localized in the mitochondria and interacted with PfExomit2 in pull-down assays. PfExomit2 also interacted with the mitochondria-targeted DSBR protein PfRad51, suggesting that it is a component of both MMR and DSBR pathways. When Exomit1 expression in the rodent parasite P. berghei was silenced in sporozoites via conditional mutagenesis, PbExomit1 conditional knockout sporozoites invaded hepatocytes and developed in the liver, but could not transition to the blood stage. PbExomit1 localized to the mitochondria in liver stages as well, indicating that its ssDNA exonuclease function in mtDNA processing in the liver impacted establishment of blood-stage infection.

Keywords:  DNA repair; Plasmodium; double‐strand break repair; exonuclease; mismatch repair; mitochondrial genome

DOI:  https://doi.org/10.1111/febs.70342
Cancer Res. 2025 Nov 17.

Mitochondrial Transfer Rescues Respiration to Support De Novo Pyrimidine Biosynthesis and Tumor Progression.

Maria Dubisova, Klara Bohacova, Zuzana Nahacka, Daniel Kraus, Jaromir Novak, Sarka Dvorakova, Petra Brisudova, Natalie Danesova, Saba Selvi, Mariia Hrysiuk, Berwini B Endaya, Panagiotis Botsios, Dan-Diem Thi Le, Monika Novotna, Sona Vodenkova, Jaroslav Truksa, Karel Chalupsky, Krystof Klima, Jan Prochazka, Radislav Sedlacek, Francesco Mengarelli, Patrick Orlando, Luca Tiano, Stepana Boukalova, Michael V Berridge, Renata Zobalova, Jiri Neuzil.

Cancer cells with severe defects in mitochondrial DNA (mtDNA) can import mitochondria via horizontal mitochondrial transfer (HMT) to restore respiration. Mitochondrial respiration is necessary for the activity of dihydroorotate dehydrogenase (DHODH), an enzyme of the inner mitochondrial membrane that catalyzes the fourth step of de novo pyrimidine synthesis. Here, we investigated the role of de novo synthesis of pyrimidines in driving tumor growth in mtDNA-deficient (ρ0) cells. While ρ0 cells grafted in mice readily acquired mtDNA, this process was delayed in cells transfected with alternative oxidase (AOX), which combines the functions of mitochondrial respiratory complexes III and IV. The ρ0 AOX cells were glycolytic but maintained normal DHODH activity and pyrimidine production. Deletion of DHODH in a panel of tumor cells completely blocked or delayed tumor growth. The grafted ρ0 cells rapidly recruited tumor-promoting/stabilizing cells of the innate immune system, including pro-tumor M2 macrophages, neutrophils, eosinophils, and mesenchymal stromal cells (MSCs). The ρ0 cells recruited MSCs early after grafting, which were potential mitochondrial donors. Grafting MSCs together with ρ0 cancer cells into mice resulted in mitochondrial transfer from MSCs to cancer cells. Overall, these findings indicate that cancer cells with compromised mitochondrial function readily acquire mtDNA from other cells in the tumor microenvironment to restore DHODH-dependent respiration and de novo pyrimidine synthesis. The inhibition of tumor growth induced by blocking DHODH supports targeting pyrimidine synthesis as a potential widely applicable therapeutic approach.

DOI: https://doi.org/10.1158/0008-5472.CAN-24-0737
DNA Repair (Amst). 2025 Nov 11. pii: S1568-7864(25)00106-5. [Epub ahead of print]156 103910

DNA G-quadruplexes: Structural and functional insights.

Sagun Jonchhe, Sudipta Lahiri, Eli Rothenberg.

  Guanine-rich regions in the human genome have the intrinsic ability to fold into G-quadruplex (G4) secondary structures, stabilized by stacked guanine quartets. There is considerable biochemical and structural evidence demonstrating formation of G4 structures in vitro under biomimetic conditions. Recently, emerging studies have also provided compelling data that authenticates the existence of these DNA G4 structures in vivo. These G4 structures, present in both DNA and RNA, are involved in key biological processes such as transcription, replication and the maintenance of genomic integrity. They have also been linked to different diseases. Given their association with multiple proteins across the DNA repair machinery, G4 structures are particularly prominent in various cancers and have been recognized as promising targets for therapeutic research. In this review, we first highlight the identification, structure and conformations of DNA G4s. We then discuss the influence of biomimetic microenvironment on G4 formation and its implication for genome function and maintenance. Next, we elaborate on the genome-wide occurrence of G4s and their roles in transcription, replication, and DNA repair. Furthermore, we explore drug design strategies aimed at selectively targeting the G4 structures and emphasize the potential of DNA G4s in cancer therapy, particularly in the context of synthetic lethality. Finally, we discuss recent advances and emerging roles of G4 biology that potentially explore new avenues of research. Taken together, this review aims to provide a comprehensive overview of DNA G4 structure and function, accentuate its role in genome maintenance and underscore their significance in cancer research.

Keywords:  Cancer; Crowding; DNA damage repair; G-quadruplex; G4-conformation; Genomic instability; Nanoconfinement; Replication; Super-resolution microscopy; Synthetic lethality; Transcription

DOI:  https://doi.org/10.1016/j.dnarep.2025.103910