Weekly reading

Weekly Papers

A rolling archive of highlighted papers from PubMed and bioRxiv, grouped by topic but kept in each week’s original reading order.

Selected week

Week 18, 2026 · 27 Apr 2026–3 May 2026

Papers

6

Status

Latest available week

Genome stability

1

Potential Rad54 separation of function mutation highlights unique roles during homologous recombination.

DNA repair paper identifying a Rad54 separation-of-function mutant that uncovers an early homologous recombination intermediate needed to stabilize D-loops.

+
Authors
Jingyi Hu, David Moraga, Amanda Xu, Lauren Peysakhova, J Brooks Crickard
Source
PubMed
Publication date
27 April 2026
Primary category
Genome stability
Priority
medium
Abstract
Homologous recombination (HR) is a DNA repair pathway that utilizes a template-based approach to repair double-strand breaks within the genome. Template use requires the exchange of individual DNA strands, which members of the RecA family of recombinases facilitate. Rad51 is a primary strand exchange factor in eukaryotes. During regular mitotic DNA repair, Rad51 is aided by the DNA translocase Rad54, which acts as a motor to remodel the template DNA and stabilize primary-strand exchange intermediates. The regulation of this activity remains incompletely understood. Here, we have identified a conserved site within the C-terminal region of Rad54. The mutation of this site creates a separation of function at early strand-exchange intermediates in vivo. Using this mutant protein, we identify a novel intermediate essential for stabilizing displacement loop (D-loop) structures. This precedes the removal of Rad51 and DNA extension. Based on our experiments, we hypothesize that this Rad54 mutant cannot stabilize Rad51-mediated strand-exchange intermediates due to slippage during translocation, leading to failure in DNA remodeling. Identifying a mutant that disrupts this intermediate before Rad51 removal unifies existing models of Rad54-mediated D-loop formation and extension.

Cancer biology

1

Paired CRISPR screens identify mitochondrial metabolism and UBE2H as aneuploid-specific dependencies in human cancer cell lines

Paired CRISPR screens identify mitochondrial metabolism and UBE2H as dependencies specific to aneuploid cancer cells.

+
Authors
Schukken, K. M., Akalu, S. M., Zou, C., Kandikuppa, P. K., Hagenson, R. A., Keane, J. L., Lynch, M. P., Yoshimoto, T., Klingbeil, O., Sausville, E. L., Mishra, S., Vakoc, C. M., Storchova, Z., Aitken, S. J., Sheltzer, J. M.
Source
bioRxiv
Publication date
28 April 2026
Primary category
Cancer biology
Priority
medium
Abstract
Aneuploidy is a hallmark of cancer and imposes widespread cellular stress, including proteotoxicity, transcriptional dysregulation, and increased metabolic demand. Although these stresses are predicted to create therapeutic vulnerabilities, the genetic dependencies of aneuploid cells remain incompletely characterized. Here, we performed paired CRISPR loss-of-function screens in isogenic aneuploid and near-euploid cancer cell line models to systematically identify aneuploidy-specific dependencies. Seven genome-wide paired screens identified ribosomes, rRNA processing, spliceosome-mediated RNA processing, proteasome subunits, and mitochondrial metabolism as top aneuploid-specific dependency gene groups. To identify therapeutically targetable aneuploid dependencies, we performed 18 additional paired CRISPR screens using a focused druggable genome library. This analysis identified the ubiquitin-conjugating enzyme UBE2H as a top aneuploid-selective dependency. Functional validation confirmed aneuploid cell dependency on UBE2H, and mechanistic analyses linked UBE2H to mitochondrial protein abundance, suggesting a role in maintaining mitochondrial proteostasis under aneuploid stress. Together, these findings define core cellular systems that support the viability of aneuploid cells and identify UBE2H as a potential therapeutic vulnerability connecting ubiquitin signaling to mitochondrial homeostasis.

Evolutionary cell biology

1

Mitochondria can spawn new 'organelles' - hinting at how modern cells evolved.

This news feature concerns mitochondria-derived organelles and the evolution of modern cells, but only a headline is available.

+
Authors
Viviane Callier
Source
PubMed
Publication date
27 April 2026
Primary category
Evolutionary cell biology
Priority
medium
Abstract
No abstract available.

CRISPR / gene editing

1

Molecular mechanisms and biotechnology applications of CRISPR-Cas12a.

This review covers Cas12a structure, guide processing, target specificity, off-target effects, and biotechnology applications.

+
Authors
Aakash Saha, Rodrigo Fregoso Ocampo, Jacquelyn T Wright, David W Taylor, Giulia Palermo
Source
PubMed
Publication date
27 April 2026
Primary category
CRISPR / gene editing
Priority
medium
Abstract
CRISPR-Cas12a is a versatile RNA-guided nuclease that has rapidly gained prominence for its dual functionality in genome editing and nucleic acid detection. In this Review, we discuss the structural, biochemical and mechanistic features of Cas12a that underpin its autonomous processing of the guide RNA and indiscriminate cleavage of single-stranded DNA, which enable Cas12a applications ranging from gene therapy to rapid diagnostics. We discuss key allosteric regulators and functional modules that orchestrate Cas12a activity, focusing on the core regulatory structural elements that control maturation of the guide RNA, target specificity, and both cis-cleavage and trans-cleavage activities, including the determinants of off-target cleavage. We provide a comparative analysis of Cas12a and the widely used Cas9, which further illuminates the distinctive attributes of Cas12a, and discuss recent advances in the characterization of its orthologues and in the development of engineered variants that expand its capabilities. Collectively, we present a comprehensive understanding of Cas12a and its increasing impact on biotechnology, therapeutics and molecular diagnostics.

AI & biology

1

The current and future landscape of AI foundation models for cancer management.

This review discusses AI foundation models for cancer management but no abstract is available.

+
Authors
Chuang Niu, Ge Wang
Source
PubMed
Publication date
28 April 2026
Primary category
AI & biology
Priority
medium
Abstract
No abstract available.

Other biology

1

Does the brain really know what word is coming next?

This is a cognitive neuroscience perspective on neural responses to language statistics, outside the tracked cell biology focus.

+
Authors
Richard J Antonello
Source
PubMed
Publication date
27 April 2026
Primary category
Other biology
Priority
low
Abstract
Apparent neural encoding of future words may arise from the statistical structure of language itself, rather than from predictive computations in the brain.