Genetics

Reported transgenerational responses to Pseudomonas aeruginosa in Caenorhabditis elegans are not robust

1. Daniel Patrick Gainey
2. Andrey V Shubin
3. Craig P Hunter

• Curated by eLife

  eLife Assessment

  This important study reports numerous attempts to replicate reports on transgenerational inheritance of a learned behavior – pathogen avoidance – in C. elegans. While the authors observe parental effects that are limited to a single generation (also called intergenerational inheritance), the authors failed to find evidence for transmission over multiple generations, or transgenerational inheritance. The experiments presented are meticulously described, making for compelling evidence that in the authors' hands transgenerational inheritance cannot be observed. There remains the possibility that different assay setups explain the failure to reproduce previous observations, although the authors present data suggesting that details of the assay are not that significant. There also remains the possibility that differences in culture conditions or lab environment explain the failure to reproduce previous observations, with updates to the paper having further reduced the probability that this applies here. Even if this were the case, it would imply that the original experimental paradigm was dependent on a very specific context. Given the prominence of the original reports of transgenerational inheritance, the present study is of broad interest to anyone studying genetics, epigenetics, or learned behavior.

  [As also pointed out by the authors of this study, the authors of the original reports have provided a response on bioRxiv (DOI: https://doi.org/10.1101/2025.01.21.634111).]

Reviewed by eLife

An H3-K9-me-independent binding of Swi6/HP1 to siRNA-DNA hybrids initiates heterochromatin assembly at cognate dg-dh repeats in Fission Yeast

1. Jyotsna Kumar
2. Swati Haldar
3. Neelima Gupta
4. Viney Kumar
5. Manisha Thakur
6. Keerthivasan Raanin Chandradoss
7. Debarghya Ghose
8. Dipak Dutta
9. Kuljeet Singh Sandhu
10. Jagmohan Singh

• Curated by eLife

  eLife Assessment

  This study aims to investigate the RNA binding activities of a conserved heterochromatin protein (Swi6) and proposes an entirely new model for how heterochromatin formation is initiated in fission yeast. While the concept is interesting, the data provided are inadequate, both for support of the claims regarding the new RNA binding activities and for support of the new model. The paper requires extensive editing as well as the inclusion of numerous experiments with appropriately controlled conditions.

Reviewed by eLife

A transcription network underlies the dual genomic coordination of mitochondrial biogenesis

1. Fan Zhang
2. Annie Lee
3. Anna V Freitas
4. Jake T Herb
5. Zong-Heng Wang
6. Snigdha Gupta
7. Zhe Chen
8. Hong Xu

• Curated by eLife

  eLife Assessment

  This study's findings substantially advance our understanding of an important aspect of mitochondrial metabolism. The data are compelling and the study is well executed. The work is relevant to all who are interested in the biogenesis of mitochondria.

Reviewed by eLife

Sir2 and Fun30 regulate ribosomal DNA replication timing via MCM helicase positioning and nucleosome occupancy

1. Carmina Lichauco
2. Eric J Foss
3. Tonibelle Gatbonton-Schwager
4. Nelson F Athow
5. Brandon Lofts
6. Robin Acob
7. Erin Taylor
8. James J Marquez
9. Uyen Lao
10. Shawna Miles
11. Antonio Bedalov

• Curated by eLife

  eLife Assessment

  This valuable study is a detailed investigation of how chromatin structure influences replication origin function in yeast ribosomal DNA, with a focus on the role of the histone deacetylase Sir2 and the chromatin remodeler Fun30. The paper shows that Sir2 does not affect origin licensing but rather affects local transcription and nucleosome positioning which correlates with increased origin firing. Overall, the evidence is convincing and the model is plausible.

Reviewed by eLife

The Drosophila maternal-effect gene abnormal oocyte ( ao ) does not repress histone gene expression

1. Risa Takenaka
2. Sierra M. Simmerman
3. Casey A. Schmidt
4. Eric H. Albanese
5. Leila E. Rieder
6. Harmit S. Malik

Reviewed by Review Commons

Systematic genetic characterization of the human PKR kinase domain highlights its functional malleability to escape a poxvirus substrate mimic

1. Michael James Chambers
2. Sophia B Scobell
3. Meru J Sadhu

• Curated by eLife

  eLife Assessment

  This important revised report describes the control of the activity of the RNA-activated protein kinase, PKR, by the Vaccinia virus K3 protein. A strength of the manuscript is the powerful combination of a classic yeast-based assay with high-throughput sequencing and its convincing experimental use to characterize large numbers of PKR variants, now with improved controls for potential biases. A minor current limitation that the authors may address in the future is the scope of the screen in terms of the segments of PKR included.

Reviewed by eLife

Prolonged cell cycle arrest in response to DNA damage in yeast requires the maintenance of DNA damage signaling and the spindle assembly checkpoint

1. Felix Y Zhou
2. David P Waterman
3. Marissa Ashton
4. Suhaily Caban-Penix
5. Gonen Memisoglu
6. Vinay V Eapen
7. James E Haber

• Curated by eLife

  eLife Assessment

  This is an important study on the damage-induced checkpoint maintenance and termination in budding yeast that provides novel and convincing evidence for a role of the spindle assembly checkpoint and mitotic exit network in halting the cell cycle after prolonged arrest in response to irreparable DNA double strand breaks (DSBs). The study identifies particular components from these checkpoints that are specifically required for the establishment and/or the maintenance of a cell cycle block triggered by such DSBs. The authors propose an interesting model for how these different checkpoints intersect and crosstalk for timely resumption of cell cycling even without repairing DNA damage that has been revised by addressing the bulk of the reviewers' comments to the first version of the manuscript.

Reviewed by eLife

DNAH3 deficiency causes flagellar inner dynein arm loss and male infertility in humans and mice

1. Xiang Wang
2. Gan Shen
3. Yihong Yang
4. Chuan Jiang
5. Tiechao Ruan
6. Xue Yang
7. Liangchai Zhuo
8. Yingteng Zhang
9. Yangdi Ou
10. Xinya Zhao
11. Shunhua Long
12. Xiangrong Tang
13. Tingting Lin
14. Ying Shen

• Curated by eLife

  eLife Assessment

  This important study identifies biallelic variants of DNAH3 in unrelated infertile men and reports infertility in DNAH3 knockout mice. The authors demonstrate that compromised DNAH3 activity decreases the expression of IDA-associated proteins in the spermatozoa of human patients and knockout mice, providing convincing evidence that DNAH3 is a novel pathogenic gene for asthenoteratozoospermia and male infertility. The study will be of substantial interest to clinicians, reproductive counselors, embryologists, and basic researchers working on infertility and assisted reproductive technology.

Reviewed by eLife

Identifying in vivo genetic dependencies of melanocyte and melanoma development

1. Sarah Perlee
2. Yilun Ma
3. Miranda V. Hunter
4. Jacob B. Swanson
5. Nelly M. Cruz
6. Zhitao Ming
7. Julia Xia
8. Timothée Lionnet
9. Maura McGrail
10. Richard M. White

• Curated by eLife

  eLife Assessment

  This important study presents a new method for generating cell-type restricted knockouts in zebrafish and it reports several interesting applications of this method to study pigmentation and melanomagenesis. The evidence supporting the conclusions is convincing, with rigorous characterization of several knock out mutations that provide a proof of principle. The work will be of broad interest to cell, skin, and cancer biologists.

Reviewed by eLife

Dimensionality reduction of genetic data using contrastive learning

1. Filip Thor
2. Carl Nettelblad

Reviewed by Arcadia Science