Search

RNA polymerase III transcribes essential non-coding RNAs, but many aspects of this biology remain unclear. Here, the authors develop DRAP3R, a nanopore sequencing method that captures Pol III transcripts and RNA modifications, revealing new RNAs and dynamic modification patterns.

Here, the authors generated and analyzed run-on sequencing data to observe transcription in species across the tree of life to uncover the origins of the promoter-proximal pause.

The bacterial genotoxin colibactin induces DNA interstrand cross-links which pose a barrier to DNA replication. Here, the authors use Xenopus egg extracts to show that the Fanconi anemia pathway is responsible for repairing these cross-links.

Authors present epigenomic, cytological, and transcriptomic evidence of a two-fold increase in transcriptome size during cotyledon photomorphogenesis, providing a paradigm shift in the study of genome regulation during plant cellular transitions.

DNA polymerase beta (Pol β) is the primary enzyme responsible for processing 1-nt gaps in chromatin during DNA repair. Here, the authors determine the kinetic and structural basis of gap-filling DNA synthesis in the nucleosome by Pol β, providing fundamental insight into DNA repair in chromatin.

The utility of CRISPR-based technologies could be enhanced with the ability to control the spatial and temporal expression of gRNAs. Here the authors design a tRNA scaffold for highly specific gRNA production from a Pol II promoter.

Incorporation of mismatched nucleotides during DNA replication or repair can lead to mutagenesis. Here the authors reveal that DNA ligase can ligate NHEJ intermediates following incorporation of 8-oxodGTP or dGTP opposite T by DNA Polymerase mu (Pol mu) in vitro, which suggests that Pol mu could cause promutagenic mismatches during DSB repair.

Intratumoral hypoxia promotes cancer progression. Here, authors show that hypoxia upregulates RNA Polymerase I activity and ribosome biogenesis in breast cancer cells and targeting RNA Polymerase I with BMH-21 reduces tumor growth and metastasis in murine models.

Oxidative stress in cells leads to the oxidations of DNA precursors. Here the authors show that these oxidized precursors can be incorporatedin vivoduring base excision repair, leading to DNA breaks and cytotoxicity.

Here, the authors implement acute factor depletion and demonstrate that the transcriptional regulator KAP1 facilitates signal-induced transcription activation by negatively regulating RNA polymerase II elongation, providing insights into the molecular underpinning of cell fate choice.

Here, using structural and biochemical data, the authors provide a comprehensive overview of Okazaki fragment maturation in Escherichia coli, demonstrating a relay of events among the involved enzymes regulating an efficient four-point molecular handover.

Three studies identify a transcription-coupled DNA–protein crosslink repair pathway that depends on the Cockayne syndrome proteins and the proteasome.

Two side-by-side papers report that the transcription elongation factor ELOF1 drives transcription-coupled repair and prevents replication stress.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

RNA polymerase III (Pol III) employs termination-associated reinitiation-recycling to express high amounts of tRNAs, which involves the essential C11 subunit. Here the authors determine the functions of various C11 domains, finding that the N-terminal domain (NTD) stimulates termination, reinitiation-recycling requires an NTD-linker, and the C-terminal domain stimulates RNA 3′-cleavage.

Cells activate various pathways to counter DNA replication stress. Using Replication-IDentifier (Repli-ID), the authors identified 423 genes, including LGE1 and ROX1, linking epigenetic and metabolic pathways to the replication stress response.

Here the authors discover that SET1 complexes function as transcription anti-termination factors that bind to CpG islands and protect low to moderately transcribed genes from the pervasive termination activity of the ZC3H4 complex.

The role of active histone modifications during zygotic genome activation (ZGA) is not fully understood in vertebrates. Here, the authors propose two types of activation mediated by different histone modifications during ZGA in teleost embryos.

RNA polymerase III (Pol III), the largest eukaryote polymerase yet characterized, transcribes structured small non-coding RNAs; here cryo-electron microscopy structures of budding yeast Pol III allow building of an atomic-level model of the complete 17-subunit complex, both unbound and while elongating RNA.

Transcription of short interspersed nuclear elements (SINEs) allows retrotransposition that contributes to chromosomal instability. Here, the authors show that methylation of histones, rather than DNA, plays a dominant role in suppressing SINE expression.

Here the authors digested chromatin with DNA fragmentation factor (DFF) prior to chromatin immunoprecipitation (DFF-ChIP) to depict transcription complex interactions with neighboring nucleosomes in cells. Applying this method to human cytomegalovirus (HMCV)-infected cells, they find that the viral genome is underchromatinized, leading to fewer transcription complex interactions with nucleosomes.

RNA polymerase (Pol) III transcribes small noncoding RNAs important in translation. Using genomics approaches, Pol III genes are now found to be in close proximity to Pol II genes and Pol III is localized to regions of active chromatin and high CpG content. One idea is that active chromatin could provide Pol III with access to the genome.

In plants, RNA-directed DNA methylation requires non-coding RNAs transcribed by RNA polymerase V (Pol V). A modified global nuclear run-on protocol and deep sequencing to capture Pol V nascent transcripts uncovered unique characteristics of Pol V RNAs.

In this work, Urem et al. characterize the mode of action as well as mechanism of reduced susceptibility related to a class of antimicrobials that is in development for the treatment of infections with Gram-positive pathogens.

Stanage et al. identify a role for transfer RNA nuclease SLFN11 in replication-stress-induced cell death in cisplatin-treated cells lacking PrimPol. SLFN11 is activated upon single-stranded DNA accumulation at stalled forks followed by replication protein A exhaustion and cell death.

Activation of an LTR retrotransposon inserted upstream of the Fgf8 gene produces viral-like particles in the mouse developing limb, triggering apoptosis and causing limb malformation. This phenotype can be rescued by mutations in the retrotransposon coding sequence.

Cryo-EM structures of Pol III preinitiation complexes are presented, comprising Pol III and the transcription factor TFIIIB bound to a natural promoter in different functional states.

Epidermal progenitors are poised for differentiation, which allows for continual balance of self-renewal and differentiation. Here they show that the Super Elongation Complex regulates this process through direct regulation of a set of rapid response genes that involves a CDK9 activity switch.

In high fidelity DNA polymerases the exonuclease site is distal from the polymerization site and it is unknown how the primer strand travels between the two sites when mis-incorporated nucleotides must be removed. Here, the authors perform MD simulations and identify an optimal path for DNA primer strand translocation in the E. coli replicative DNA polymerase III and characterise the kinetics and dynamics of the Pol III pol-to-exo mode transition, which is validated with mutagenesis experiments.

Researchers demonstrate that Bell's measure — a commonly used test of quantum nonlocality — can be used in classical optical schemes to separate incoherence associated with statistical fluctuations from incoherence based on correlation. This technique may be useful for quantum information applications such as classical optical coherence theory and optical signal processing.

Mediator is the key transcription co-activator complex that enables basal and regulated transcription initiation by RNA polymerase (Pol) II; here a 15-subunit yeast core Mediator bound to a core Pol II initiation complex is reconstituted and its structure determined by cryo-electron microscopy at subnanometre resolution.

How DNA polymerases discriminate against oxidized and undamaged nucleotides during DNA repair is not fully understood. Here, the authors reveal high-resolution timelapse X-ray crystallography snapshots of DSB repair polymerase μ undergoing DNA synthesis providing mechanistic insights into the process.

DNA polymerase (pol) λ performs DNA synthesis in base excision and double strand break repair. How pol λ accomplishes nucleotide insertion that can lead to mutagenesis and genomic instability was unclear. Here the authors employ time-lapse crystallography to reveal hidden polymerase checkpoints that enable right and wrong natural nucleotide insertion by pol λ.

Epigenome editing programs gene silencing without inducing DNA breaks but challenges in delivery into human cells limit its broader use. Here, the authors present the RENDER platform, which uses virus-like particles to enable CRISPR-based epigenome editing for durable gene silencing in human cells.

Targeting FSP1 in lymph nodes has considerable potential for blocking melanoma progression.

DNA polymerase (pol) μ functions in DNA double-strand break repair. Here the authors use time-lapse X-ray crystallography to capture the states of pol µ during the conversion from pre-catalytic to product complex and observe a third transiently bound metal ion in the product state.

Establishment of biological sex involves differentiation of the primary gonad, which is biased towards ovarian fates in many species. Here they show that the RNA binding protein Rbpms2 acts as a repressor of “testis” RNAs in oocytes and identify an oocyte progression checkpoint regulated by Rbpms2 and the Gator2 protein, Mios.

Combination immunotherapy approaches might be effective in inducing sustained control of HIV by slowing rebound and improving CD8⁺ T cell responses.

Transcription initiation involves recruitment of key factors to promoters. Yeast TATA-binding protein (TBP) turnover is now examined genome-wide and genes transcribed by the three RNA polymerases found to have distinct signatures. Further analyses suggest that TBP dynamics, rather than DNA sequence affinity per se, is key to gene expression.

Using a non-human primate model, the authors identified the tissue sites of initial viral rebound after discontinuation of antiretroviral therapy, demonstrating that such rebound preferentially occurs in the gastrointestinal tract-associated lymphoid tissues.

Oxidative stress is a common source of DNA damage and is repaired by the base excision repair machinery, including polymerase beta. Here the authors find that polymerase beta, and to a lesser extent lambda, can mistakenly incorporate ribonucleotides during synthesis.

CX-5461 recently progressed through phase I clinical trial as a first-inhuman inhibitor of RNA-POL I. Here, the authors demonstrate that CX-5461 synergizes with topoisomerase I inhibitors to inhibit neuroblastoma cells and that its primary target in this disease is topoisomerase II beta and not RNA-POL I.

A machine-learning-potential framework achieves an optimal balance of accuracy and efficiency through monomeric decomposition. Systematic evaluations highlight its potential in large-scale simulations of complex molecular systems.

Kofuji et al. demonstrate that upregulation of IMPDH2 promotes nucleostemin stabilization and nucleoli malformation, and its inactivation induces growth arrest in glioblastoma.

Membrane receptor kinases are involved in many signalling pathways in plants. Here, the authors show that a common mechanism, consisting of a RLCK kinase and a PP2C phosphatase, regulates signalling downstream of receptors, both in immunity and development.