Molecular biology articles from across Nature Portfolio

Repetitive sequences make extrachromosomal DNA vulnerable to breaks, which could be exploited for therapy — but might also promote tumour evolution.

Advances in phosphoproteomics enable systems-wide mapping of phosphorylation, but translating these data into functional signaling networks remains challenging. A deep human cell-line phosphoproteome atlas infers kinase activity, enabling systematic network mapping and identification of actionable kinase vulnerabilities for precision therapies.

Replication stress often induces fork reversal, which protects stalled replication intermediates until replication can resume. This study identifies the ATM kinase as a key regulator that promotes nuclease-dependent processing of reversed fork structures formed at DNA interstrand cross-links.

Häkkinen et al. show that zebrafish neural crest cells encounter increased tissue-scale confinement along the body axis. Despite nuclear deformation, migrating neural crest cells experience neither nuclear envelope rupture nor increased DNA damage.

We investigated how the individual domains of the histone variant macroH2A regulate nucleosome structure, chromatin remodelling, and chromatin compaction using biochemical, biophysical, mutagenesis, and cryo-EM approaches. We found that the macroH2A histone fold, particularly its C-terminal tail, restricts entry/exit DNA dynamics and inhibits ATP-dependent chromatin remodeling, while the linker region synergizes with linker histone H1 to promote chromatin compaction, revealing complementary mechanisms by which macroH2A reinforces repressive chromatin.

The dark proteome encompasses previously undiscovered and uncharacterized protein molecules derived from alternative genomic loci or altered RNA translation. In this Perspective, Prensner et al. describe the current understanding of the dark proteome and set out the critical questions that need to be addressed in the field to determine whether the dark proteome can fulfill its potential for clinical translation.

Repetitive sequences make extrachromosomal DNA vulnerable to breaks, which could be exploited for therapy — but might also promote tumour evolution.

In this Tools of the Trade article, Wang (Cosma Lab) and Zhang (Hongyan Sun Lab) describe the development of self-blinking HoT probes that are compatible with super-resolution microscopy and can be used to resolve nuclear architecture and chromatin.

Advances in phosphoproteomics enable systems-wide mapping of phosphorylation, but translating these data into functional signaling networks remains challenging. A deep human cell-line phosphoproteome atlas infers kinase activity, enabling systematic network mapping and identification of actionable kinase vulnerabilities for precision therapies.