Genetics

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

Dimensionality reduction of genetic data using contrastive learning

1. Filip Thor
2. Carl Nettelblad

Reviewed by Arcadia Science

Sibling similarity can reveal key insights into genetic architecture

1. Tade Souaiaia
2. Hei Man Wu
3. Clive Hoggart
4. Paul F O'Reilly

• Curated by eLife

  eLife assessment

  The authors present a solid statistical framework for using sibling phenotype data to assess whether there is evidence for de-novo or rare variants causing extreme trait values. Their valuable method is promising and will be of interest to researchers studying complex trait genetics.

Reviewed by eLife

Single-cell eQTL mapping in yeast reveals a tradeoff between growth and reproduction

1. James Boocock
2. Noah Alexander
3. Leslie Alamo Tapia
4. Laura Walter-McNeill
5. Shivani Prashant Patel
6. Chetan Munugala
7. Joshua S Bloom
8. Leonid Kruglyak

• Curated by eLife

  eLife assessment

  This manuscript describes the mapping of natural DNA sequence variants that affect gene expression and its noise, as well as cell cycle timing, using as input single-cell RNA-sequencing of progeny from crosses between wild yeast strains. The method represents an important advance in the study of natural genetic variation. The findings, especially given the follow-up validation of the phenotypic impact of a mapped locus of major effect, provide convincing support for the rigor and utility of the method.

Reviewed by eLife, Arcadia Science

Transcription factor condensates, 3D clustering, and gene expression enhancement of the MET regulon

1. James Lee
2. Leman Simpson
3. Yi Li
4. Samuel Becker
5. Fan Zou
6. Xin Zhang
7. Lu Bai

• Curated by eLife

  eLife assessment

  This important study investigates the relationship between transcription factor condensate formation, transcription, and 3D gene clustering of the MET regulon in the model organism S. cerevisiae. The authors provide solid experimental evidence that transcription factor condensates enhance transcription of MET-regulated genes, but evidence for the role of Met4 IDRs and Met4-containing condensates in mediating target gene clustering in the MET regulon is not as strong. This paper will be of interest to molecular biologists working on chromatin and transcription, although its impact would be strengthened by further investigation.

Reviewed by eLife

Tbx1 haploinsufficiency causes brain metabolic and behavioral anomalies in adult mice which are corrected by vitamin B12 treatment

1. Marianna Caterino
2. Debora Paris
3. Giulia Torromino
4. Michele Costanzo
5. Gemma Flore
6. Annabella Tramice
7. Elisabetta Golini
8. Silvia Mandillo
9. Diletta Cavezza
10. Claudia Angelini
11. Margherita Ruoppolo
12. Andrea Motta
13. Elvira De Leonibus
14. Antonio Baldini
15. Elizabeth Illingworth
16. Gabriella Lania

Reviewed by Review Commons

A CRISPR-Cas9-based system for the dose-dependent study of DNA double-strand breaks sensing and repair

1. Jocelyn Coiffard
2. Sylvain Kumanski
3. Olivier Santt
4. Benjamin Pardo
5. María Moriel-Carretero

Reviewed by Review Commons

Resetting of H3K4me2 during mammalian parental-to-zygote transition

1. Chong Wang
2. Yong Shi
3. Jia Guo
4. Kaiyue Hu
5. Yaqian Wang
6. Yang Li
7. Jiawei Xu

• Curated by eLife

  eLife assessment

  This study presents an important finding of dynamic reprogramming of global H3K4me2 during mouse oocyte-to-embryo transition. While the H3K4me2 epigenome data is convincing, the interpretation and the potential mechanistic claims of the authors are incomplete in the current shape with the primary concerns regarding the contribution of Kdm1b or Kdm1a, as well as the specificity of the inhibitor and the antibody. The work will be of interest to researchers interested in epigenetic reprogramming.

Reviewed by eLife