Molecular Biology

Structural mechanism of strand exchange by the RAD51 filament

1. Luay Joudeh
2. Robert E Appleby
3. Joseph D Maman
4. Luca Pellegrini

• Curated by eLife

  eLife Assessment

  This landmark study describes the structure of the human RAD51 filament with a recombination intermediate called the displacement loop (D-loop). Using cryogenic structural, biochemical, and single-molecule analyses, the authors provide compelling evidence on how the RAD51 filament promotes strand exchange between single-stranded and double-stranded DNAs. The findings are highly relevant to the fields of homologous recombination, DNA repair, and genome stability.

Reviewed by eLife

Molecular Landscape of the Mouse Adrenal Gland and Adjacent Adipose by Spatial Transcriptomics

1. Małgorzata Blatkiewicz
2. Szymon Hryhorowicz
3. Marta Szyszka
4. Joanna Suszyńska-Zajczyk
5. Andrzej Pławski
6. Adam Plewiński
7. Andrea Porzionato
8. Ludwik K Malendowicz
9. Marcin Rucinski

• Curated by eLife

  eLife Assessment

  This useful study provides a spatial transcriptomic analysis of the mouse adrenal gland that could have implications for future research and applications. The authors present solid results that allow the dissection of the cell signalling pathways and cellular composition of different zones of the adrenal glands in the mouse model; they propose new zone-specific gene markers and specific intra- and inter-zonal signaling pathways based on receptor-ligand expression patterns. Their web tool is user-friendly and will be helpful for adrenal scientists; however, the validation of crucial results of the large dataset is necessary. There are also several contradictory results/interpretations, and the opportunity to dissect the sexually dimorphic gene expression pattern and mouse-human interspecies differences is a missed opportunity.

Reviewed by eLife

ADMA-histones play a crucial role in the initial recognition of dual-strand piRNA cluster regions by Rhino

1. Raku Saito
2. Hirotsugu Ishizu
3. Ritsuko Harigai
4. Kensaku Murano
5. Yurika Namba
6. Mikiko C Siomi

• Curated by eLife

  eLife Assessment

  This valuable study identifies asymmetric dimethylarginine (ADMA) histones as potential determinants of the initial genomic binding of Rhino, a Drosophila-specific chromatin protein essential for piRNA cluster specification. The authors provide correlative genomic and imaging data to support their model, although functional validation of the proposed mechanism remains incomplete. The authors could revise the manuscript to reflect that they have uncovered a small subset of piRNA clusters dependent on ADMA-histones, which may not be the general rule.

Reviewed by eLife

Molecular interactome of HNRNPU reveals regulatory networks in neuronal differentiation and DNA methylation

1. Marika Oksanen
2. Francesca Mastropasqua
3. Krystyna Mazan-Mamczarz
4. Jennifer L. Martindale
5. Xuan Ye
6. Abishek Arora
7. Nirad Banskota
8. Myriam Gorospe
9. Kristiina Tammimies

Reviewed by preLights

Boltz-2: Towards Accurate and Efficient Binding Affinity Prediction

1. Saro Passaro
2. Gabriele Corso
3. Jeremy Wohlwend
4. Mateo Reveiz
5. Stephan Thaler
6. Vignesh Ram Somnath
7. Noah Getz
8. Tally Portnoi
9. Julien Roy
10. Hannes Stark
11. David Kwabi-Addo
12. Dominique Beaini
13. Tommi Jaakkola
14. Regina Barzilay

Reviewed by PREreview

Srs2 binding to proliferating cell nuclear antigen (PCNA) and its sumoylation contribute to replication protein A (RPA) antagonism during the DNA damage response

1. Jiayi Fan
2. Nalini Dhingra
3. Tammy Yang
4. Vicki Yang
5. Xiaolan Zhao

• Curated by eLife

  eLife Assessment

  This manuscript reports valuable findings on the role of the Srs2 protein in turning off the DNA damage signaling response initiated by Mec1 (human ATR) kinase. The data provide convincing evidence that Srs2 interaction with PCNA and ensuing SUMO modification is required for checkpoint downregulation. However, while the model that Srs2 acts at gaps after camptothecin-induced DNA damage is reasonable, direct experimental evidence for this is currently lacking. The work will be of interest to cell biologists studying genome integrity.

Reviewed by eLife

EPB41L4A-AS1 long noncoding RNA acts in both cis- and trans-acting transcriptional regulation and controls nucleolar biology

1. Alan Monziani
2. Juan Pablo Unfried
3. Todor Cvetanovic
4. Igor Ulitsky

• Curated by eLife

  eLife Assessment

  The work provides important insights into how this lncRNA regulates gene expression via complex mechanisms, however, the biological relevance awaits validation in other models. This paper provides extensive and carefully analysed data that is of value in efforts to understand the role of the lncRNA EPB41L4A-AS1 in a human cell line. The data is generally convincing and supported by clever integrative analysis; however, the known extensive artefacts from individual Gapmer oligonucleotides cast some doubt over the interpretation of those experiments where only one targeting and one control Gapmer are used.

Reviewed by eLife

Human eIF2A has a minimal role in translation initiation and in uORF-mediated translational control in HeLa cells

1. Mykola Roiuk
2. Marilena Neff
3. Aurelio A Teleman

• Curated by eLife

  eLife Assessment

  In this valuable study, Roiuk et al combined ribosome profiling and reporter assays to provide compelling evidence that eIF2A does not have a major impact on mRNA translation in HeLa cells. These findings are consistent with several recent publications that disaffirm the previously proposed role of eIF2A in directing protein synthesis under stress. Considering that stress-dependent perturbations in translation play a major role in homeostasis and several pathological states (e.g., cancer and neurological disorders), this work should be of broad interest to researchers studying regulation of gene expression, stress-adaptation, cancer and neurobiology.

Reviewed by eLife

The molecular logic of Gtr1/2- and Pib2-dependent TORC1 regulation in budding yeast

1. Jacob H Cecil
2. Cristina M Padilla
3. Austin A Lipinski
4. Paul Langlais
5. Xiangxia Luo
6. Andrew P Capaldi

• Curated by eLife

  eLife assessment

  The study presents valuable findings concerning how a highly conserved signal transduction pathway helps budding yeast cells adapt their growth to nitrogen sources of differing qualities. However, the evidence is incomplete for the authors' main claim that the pathway adopts three distinct states depending on the nitrogen source. The presented data, particularly phospho-proteomic datasets, will be of interest to the cell growth signaling community.

Reviewed by eLife

Nucleoplasmic Lamin A/C controls replication fork restart upon stress by modulating local H3K9me3 and ADP-ribosylation levels

1. Veronica Cherdyntseva
2. Joanna Paulson
3. Selin Adakli
4. Jean-Philippe Gagné
5. Moses Aouami
6. Patricia Ubieto-Capella
7. Daniel González-Acosta
8. Collin Bakker
9. Guy G. Poirier
10. Nitika Taneja
11. Massimo Lopes

Reviewed by preLights