Genetics

DNA replication in primary hepatocytes without the six-subunit ORC

1. Róża K Przanowska
2. Yuechuan Chen
3. Takayuki-Okano Uchida
4. Etsuko Shibata
5. Xiaoxiao Hao
6. Isaac Segura Rueda
7. Kate Jensen
8. Piotr Przanowski
9. Anthony Trimboli
10. Yoshiyuki Shibata
11. Gustavo Leone
12. Anindya Dutta

• Curated by eLife

  eLife Assessment

  This valuable descriptive manuscript builds on prior research showing that the elimination of Origin Recognition Complex (ORC) subunits does not halt DNA replication. The authors obtain solid data using various methods to genetically remove one or two ORC subunits from specific tissues and still observe replication. The replication appears to be primarily endoreduplication, indicating that ORC-independent replication may promote genome reduplication without mitosis. The mechanism behind this ORC-independent replication remains to be elucidated. The study and mutants described herein lay the groundwork for future research to explore how cells compensate for the absence of ORC and to develop functional approaches to investigate this process. The reviewers suggested the observations could be supported by additional experiments. This work will be of interest to those studying genome duplication and replication.

Reviewed by eLife, Review Commons

Proteostasis modulates gene dosage evolution in antibiotic-resistant bacteria

1. Chinmaya Jena
2. Saillesh Chinnaraj
3. Soham Deolankar
4. Nishad Matange

• Curated by eLife

  eLife Assessment

  This important study explores the interplay between gene dosage and gene mutations in the evolution of antibiotic resistance. The authors provide compelling evidence connecting proteostasis with gene duplication during experimental evolution in a model system. This paper is likely to be of interest to researchers studying antibiotic resistance, proteostasis, and bacterial evolution.

Reviewed by eLife

Neanderthal-derived variants shape craniofacial enhancer activity at a human disease locus

1. Kirsty Uttley
2. Hannah J Jüllig
3. Carlo De Angelis
4. Julia MT Auer
5. Ewa Ozga
6. Hemant Bengani
7. Hannah K Long

Reviewed by Review Commons

A genome-wide association study implicates the olfactory system in Drosophila melanogaster diapause-associated lifespan extension and fecundity

1. Sreesankar Easwaran
2. Denise J Montell

• Curated by eLife

  eLife Assessment

  This important study shows how genetic variation is associated with fecundity following a period of reproductive diapause in female Drosophila. The work identifies the olfactory system as central to successful diapause with associated changes in longevity and fecundity. While the methods used are convincing, a limitation of the study, as of any other laboratory-based investigation is the challenge of demonstrating how well measures for fitness related to diapause and its recovery correlates with realities encountered during development in the wild.

Reviewed by eLife

UBR-1 deficiency leads to ivermectin resistance in Caenorhabditis elegans

1. Yi Li
2. Long Gong
3. Jing Wu
4. Wesley Hung
5. Mei Zhen
6. Shangbang Gao

• Curated by eLife

  eLife Assessment

  This important study allows for a better understanding of anthelmintic drug resistance in nematodes. The authors provide a detailed analysis of the role of UBR-1 and its underlying mechanism in ivermectin resistance using convincing behavioural and genetic experiments with C. elegans. Although the authors have addressed the concerns of the reviewers, it would be prudent for the authors to disclose the Dyf phenotype in ubr-1 mutants. The authors should at the very least report the Dyf phenotype and the experiment on which they base the argument that the Dyf phenotype does not affect their conclusions.

Reviewed by eLife

Becker muscular dystrophy mice showed site-specific decay of type IIa fibers with capillary change in skeletal muscle

1. Daigo Miyazaki
2. Mitsuto Sato
3. Naoko Shiba
4. Takahiro Yoshizawa
5. Akinori Nakamura

• Curated by eLife

  eLife Assessment

  The authors present three transgenic models carrying three representative exon deletions of the dystrophin gene. The findings presented are valuable to the field of muscle diseases, particularly muscular dystrophies. The evidence provided in the manuscript is convincing, with rigorous biochemical assays and state-of-the-art microscopy methods.

Reviewed by eLife

Regeneration following tissue necrosis is mediated by non-apoptotic caspase activity

1. Jacob W Klemm
2. Chloe Van Hazel
3. Robin E Harris

• Curated by eLife

  eLife Assessment

  This manuscript reports fundamental discoveries on how necrotic cells contribute to organ regeneration through apoptotic signalling to produce cells with non-lethal apoptotic caspase activity that contribute to the regenerated tissue. These findings will be of broad interest to those who study wound repair and tissue regeneration. The strength of the evidence is solid and has been improved in the revised version.

Reviewed by eLife

The domesticated transposon protein L1TD1 associates with its ancestor L1 ORF1p to promote LINE-1 retrotransposition

1. Gülnihal Kavaklioglu
2. Alexandra Podhornik
3. Terezia Vcelkova
4. Jelena Marjanovic
5. Mirjam A Beck
6. Trinh Phan-Canh
7. Theresia Mair
8. Claudia Miccolo
9. Aleksej Drino
10. Mirko Doni
11. Gerda Egger
12. Susanna Chiocca
13. Miha Modic
14. Christian Seiser

• Curated by eLife

  eLife Assessment

  This important paper reports functional interactions between L1TD1, an RNA binding protein (RBP), and its ancestral LINE-1 retrotransposon which is not modulated at the translational level. The evidence for the association between L1TD1 and LINE-1 ORF1p is solid. The work implies that the transposon-derived RNA binding protein in the human genome can interact with the ancestral transposable element from which this protein was initially derived. This work spurs interesting questions for cancer types, where LINE1 and L1TD1 are aberrantly expressed.

Reviewed by eLife

Deficiency in DNAH12 causes male infertility by impairing DNAH1 and DNALI1 recruitment in humans and mice

1. Menglei Yang
2. Hafiz Muhammad Jafar Hussain
3. Manan Khan
4. Zubair Muhammad
5. Jianteng Zhou
6. Ao Ma
7. Xiongheng Huang
8. Jingwei Ye
9. Min Chen
10. Aoran Zhi
11. Tao Liu
12. Ranjha Khan
13. Ali Asim
14. Wasim Shah
15. Aurang Zeb
16. Nisar Ahmad
17. Huan Zhang
18. Bo Xu
19. Hui Ma
20. Qinghua Shi
21. Baolu Shi

• Curated by eLife

  eLife Assessment

  This fundamental study further validates DNAH12 as a causative gene for asthenoteratozoospermia and male infertility in both humans and mice. Compelling evidence supports the notion that DNAH12 is essential for proper axonemal development. This work will be of interest to reproductive biologists studying spermatogenesis and sperm biology, as well as andrologists focusing on male fertility.

Reviewed by eLife

Impact of liver-specific survival motor neuron (SMN) depletion on central nervous system and peripheral tissue pathology

1. Monique Marylin Alves de Almeida
2. Yves De Repentigny
3. Sabrina Gagnon
4. Emma R Sutton
5. Rashmi Kothary

• Curated by eLife

  eLife Assessment

  This work presents an important mouse model for a liver-specific depletion of the Survival Motor Neuron (SMN) protein, where the liver retains 30% of functional full-length SMN protein. The authors provide a profile of phenotypic changes in liver-specific SMN depleted mice with convincing evidence supporting their claims.

Reviewed by eLife