Molecular Biology

ATP induced conformational change of axonemal outer dynein arms studied by cryo-electron tomography

1. Noemi Zimmermann
2. Akira Noga
3. Jagan Mohan Obbineni
4. Takashi Ishikawa

Reviewed by Review Commons

The ADAM17 sheddase complex regulator iTAP/Frmd8 modulates inflammation and tumor growth

1. Marina Badenes
2. Emma Burbridge
3. Ioanna Oikonomidi
4. Abdulbasit Amin
5. Érika de Carvalho
6. Lindsay Kosack
7. Camila Mariano
8. Pedro Domingos
9. Pedro Faísca
10. Colin Adrain

Reviewed by Review Commons

The establishment of variant surface glycoprotein monoallelic expression revealed by single-cell RNA-seq of Trypanosoma brucei in the tsetse fly salivary glands

1. Sebastian Hutchinson
2. Sophie Foulon
3. Aline Crouzols
4. Roberta Menafra
5. Brice Rotureau
6. Andrew D. Griffiths
7. Philippe Bastin

• Curated by eLife

  Evaluation Summary:

  All reviewers think the study will be really valuable for the field, especially after re-writing to include a detailed comparison with results that were previously published. We all appreciate the clear identification of a gamete sub-population, and also thought that the discovery of low activation of all VSG expression sites was intriguing and will be of considerable interest to those 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. The reviewers all agreed to share their names with the authors.)

Reviewed by eLife

Antisense non-coding transcription represses the PHO5 model gene at the level of promoter chromatin structure

1. Ana Novačić
2. Dario Menéndez
3. Jurica Ljubas
4. Slobodan Barbarić
5. Françoise Stutz
6. Julien Soudet
7. Igor Stuparević

Reviewed by Review Commons

Multiple UBX proteins reduce the ubiquitin threshold of the mammalian p97-UFD1-NPL4 unfoldase

1. Ryo Fujisawa
2. Cristian Polo Rivera
3. Karim PM Labib

• Curated by eLife

  Evaluation Summary:

  This paper describes a biochemical analysis of the roles of Ub chain length on Ub-dependent segregase activity of yeast and human p97 and the role of UBX proteins on the disassembly of the CMG replicative helicase complex. The human p97 complex does not segregate substrates with shorter ubiquitin chains as efficiently as does the yeast complex but the human complex can be enhanced in vitro by 3 UBX proteins - FAF1, FAF2, and UBXN7. Cellular studies indicate a partial role for FAF1 and UBXN7 in cells. The paper would be strengthened by additional mechanistic understanding of how the UBX domain functions in activation of segregase activity and the contribution of this pathway in cells.

  (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

The termination of UHRF1-dependent PAF15 ubiquitin signaling is regulated by USP7 and ATAD5

1. Ryota Miyashita
2. Atsuya Nishiyama
3. Weihua Qin
4. Yoshie Chiba
5. Satomi Kori
6. Norie Kato
7. Chieko Konishi
8. Soichiro Kumamoto
9. Hiroko Kozuka-Hata
10. Masaaki Oyama
11. Yoshitaka Kawasoe
12. Toshiki Tsurimoto
13. Tatsuro S Takahashi
14. Heinrich Leonhardt
15. Kyohei Arita
16. Makoto Nakanishi

• Curated by eLife

  Evaluation Summary:

  DNA methylation inheritance through the UHRF1-DNMT1 signaling axis is becoming increasingly appreciated as a ubiquitin-regulated process. This study builds on the observation that UHRF1 multi mono-ubiquitinates the PCNA-associated protein PAF15, and that, similarly to H3 substrates, these mono-ubiquitin sites are bound by DNMT1 and may contribute to its S-phase chromatin association. The authors focus on players involved in ubiquitin removal and PAF15 release from chromatin and they identify the deubiquitinase USP7 and the DNA replication regulator ATAD5 as important to this termination process. While manipulation of these factors using Xenopus egg extracts shows quite striking effects on DNMT1 chromatin association, effects on DNA methylation are minimal and this brings to question the importance and potential impact of the pathway involving PAF15. In addition, how the findings from Xenopus egg extracts translate to regulation of DNA methylation maintenance in mammalian cells is currently unclear.

  (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

Chaperone requirements for de novo folding of Saccharomyces cerevisiae septins

1. Daniel Hassell
2. Ashley Denney
3. Emily Singer
4. Aleyna Benson
5. Andrew Roth
6. Julia Ceglowski
7. Marc Steingesser
8. Michael McMurray

Reviewed by Review Commons

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