Molecular Biology

Global chromatin mobility induced by a DSB is dictated by chromosomal conformation and defines the HR outcome

1. Fabiola García Fernández
2. Etienne Almayrac
3. Ànnia Carré Simon
4. Renaud Batrin
5. Yasmine Khalil
6. Michel Boissac
7. Emmanuelle Fabre

• Curated by eLife

  Evaluation Summary:

  This study is of relevance to the field of DNA repair. It uses a cleverly designed new recombination assay in yeast to address the impact of DNA break position on global genome mobility. A centromere-proximal DNA double-strand break (DSB) induces an H2A(X) phosphorylation-dependent global mobility that accelerates but is not essential for DSB repair, while a centromere-distal DSB triggers global mobility that is essential for repair and which depends on H2A(X) phosphorylation, Rad9 and Rad51. Together, these data support a model where global genome mobility promotes homologous recombination repair, particularly for centromere-distal DSBs, and help settle some recent controversy in the field.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Polycomb-mediated repression of paternal chromosomes maintains haploid dosage in diploid embryos of Marchantia

1. Sean Akira Montgomery
2. Tetsuya Hisanaga
3. Nan Wang
4. Elin Axelsson
5. Svetlana Akimcheva
6. Milos Sramek
7. Chang Liu
8. Frédéric Berger

• Curated by eLife

  Evaluation Summary:

  Mechanisms for controlling gene dosage and uniparental gene expression vary widely across the eukaryotic tree, with many such mechanisms still unknown. Montgomery et al. describe an epigenetic mechanism used to modulate paternal chromosome gene dosage during the transient diploid state of the primarily haploid plant, Marchantia polymorpha. This fascinating case of genome-wide genomic imprinting will be of broad interest to evolutionary biologists, epigeneticists, and those focused on understanding the context and mechanisms of gene dosage control.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Polysome-CAGE of TCL1-driven chronic lymphocytic leukemia revealed multiple N-terminally altered epigenetic regulators and a translation stress signature

1. Ariel Ogran
2. Tal Havkin-Solomon
3. Shirly Becker-Herman
4. Keren David
5. Idit Shachar
6. Rivka Dikstein

• Curated by eLife

  Evaluation Summary:

  In this study, Ogran and colleagues provide evidence suggesting that T-Cell Leukemia/Lymphoma 1 (TCL1) protein may promote alternative transcription site selection and promoter usage in chronic lymphoid leukemia. It is further proposed that these TCL1-dependent alterations lead to the production of N-terminally truncated versions of proteins including chromatin regulators while bolstering expression of transcription factors including MYC. Collectively, it was found that these results are of broad interest inasmuch as they suggest previously unappreciated rewiring of epigenetic, transcriptional, and translational programs in leukemic cells. To this end, this article should be of significant interest across a variety of fields of biomedical research ranging from regulation of gene expression to cancer research. The paper would be strengthened by mechanistic data linking TCL1 to alterations in transcription site selection and/or alternative promoter usage and by stronger validation of the expression of N-truncated proteins and their functional consequences.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Distinct elongation stalls during translation are linked with distinct pathways for mRNA degradation

1. Anthony J Veltri
2. Karole N D'Orazio
3. Laura N Lessen
4. Raphael Loll-Krippleber
5. Grant W Brown
6. Rachel Green

• Curated by eLife

  Evaluation Summary:

  This manuscript will interest a large community of molecular biologists studying translation and mRNA decay. The study provides a large-scale comparison of the roles of protein factors in No-Go Decay (NGD) and Codon-Optimality-Mediated Decay (COMD) in the yeast S. cerevisiae. A major strength of the manuscript is the direct comparison between one mRNA with a single strong translational stall and another similar mRNA with many slow translation sites (caused by changes in the genetic code). The analysis of both the factors that cause decay of these mRNAs as well as the ribosome states on the different mRNAs has the potential to reveal the molecular basis for the different mechanisms of mRNA quality control.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Large protein complex interfaces have evolved to promote cotranslational assembly

1. Mihaly Badonyi
2. Joseph A Marsh

• Curated by eLife

  Evaluation Summary:

  The authors use a combination of proteome-specific protein complex structures and publicly available ribosome profiling data to show that cotranslational assembly is favored by large N-terminal intermolecular interfaces. The manuscript represents an important contribution to the field of protein biosynthesis pathways by suggesting an intuitive evolutionary mechanism that can promote co-translational assembly pathways in mammalians, yeast, and bacteria.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Anti-COVID-19 Activity of FDA Approved Drugs through RNA G-quadruplex Binding

1. Shuvra Shekhar Roy
2. Shalu Sharma
3. Zaigham Abbas Rizvi
4. Dipanjali Sinha
5. Divya Gupta
6. Mercy Rophina
7. Paras Sehgal
8. Srikanth Sadhu
9. Manas Ranjan Tripathy
10. Sweety Samal
11. Souvik Maiti
12. Vinod Scaria
13. Sridhar Sivasubbu
14. Amit Awasthi
15. Krishnan H Harshan
16. Sanjeev Jain
17. Shantanu Chowdhury

Reviewed by ScreenIT

Multistep loading of a DNA sliding clamp onto DNA by replication factor C

1. Marina Schrecker
2. Juan C Castaneda
3. Sujan Devbhandari
4. Charanya Kumar
5. Dirk Remus
6. Richard K Hite

• Curated by eLife

  Evaluation Summary:

  This study is of relevance to the field of DNA replication, describing how an ATPase known as a 'clamp loader' opens a ring-shaped clamp protein and binds DNA to promote the deposition of the clamp around a nucleic acid duplex to support chromosomal replication. The findings on how different regions of the clamp loader bind to and open a clamp, and how the enzyme engages single-stranded and double-stranded regions of target DNAs provide new insights that further our understanding of the clamp loading reaction. It is intriguing that the clamp loader melts the end of the DNA duplex, an activity that had not been observed before or predicted.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Spatial modeling reveals nuclear phosphorylation and subcellular shuttling of YAP upon drug-induced liver injury

1. Lilija Wehling
2. Liam Keegan
3. Paula Fernández-Palanca
4. Reham Hassan
5. Ahmed Ghallab
6. Jennifer Schmitt
7. Yingyue Tang
8. Maxime Le Marois
9. Stephanie Roessler
10. Peter Schirmacher
11. Ursula Kummer
12. Jan G Hengstler
13. Sven Sahle
14. Kai Breuhahn

• Curated by eLife

  Evaluation Summary:

  The authors made an important extension of the canonical Hippo pathway by showing that nuclear phosphorylation of the pathway components YAP/TAZ contributes to the shuttling between different cellular compartments. The conclusions are well supported by the experimental evidence under both physiological and tissue-damaging conditions. Given the importance and developmental conserveness of the Hippo pathway, the work is of broad interest to the field of developmental and regenerative biology.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Unleashing a novel function of Endonuclease G in mitochondrial genome instability

1. Sumedha Dahal
2. Humaira Siddiqua
3. Shivangi Sharma
4. Ravi K Babu
5. Diksha Rathore
6. Sheetal Sharma
7. Sathees C Raghavan

• Curated by eLife

  Evaluation Summary:

  This manuscript is of interest for researchers in the field of mitochondrial genome stability and mitochondrial genetic diseases. The authors show that endonuclease G preferentially binds to mitochondrial genome regions which have a potential for forming G4 tetraplexes, inducing DNA breaks that may lead to a common 9 bp deletion in the mitochondrial genome by microhomology-mediated endjoining.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

GDF15 and ACE2 stratify COVID19 patients according to severity while ACE2 mutations increase infection susceptibility

1. Margalida Torrens-Mas
2. Catalina M Perelló-Reus
3. Neus Trias-Ferrer
4. Lesly Ibargüen-González
5. Catalina Crespí
6. Aina Maria Galmes-Panades
7. Cayetano Navas-Enamorado
8. Andres Sanchez-Polo
9. Javier Piérola-Lopetegui
10. Luis Masmiquel
11. Lorenzo Socias Crespi
12. Carles Barcelo
13. Marta Gonzalez-Freire

Reviewed by ScreenIT