Molecular cellNov 21, 2025

Body Clock Proteins Help Repair DNA Damage by Anchoring to the Cell’s Nucleus

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Circadian PERIOD proteins help route transcription-coupled DNA double-strand break repair to the nuclear envelope in human cells.

Evidence

This mechanistic human-cell study used screening and repair assays to identify PERIOD-complex effects on PER2 recruitment, nuclear-envelope docking, RAD51 assembly, and DSB clustering.

Caveat

The chrono-chemotherapy implications are inferred from cell-based repair mechanisms rather than tested treatment outcomes.

Simplified

Repair of DNA double-strand breaks (DSBs) produced in transcriptionally active chromatin occurs through a poorly characterized pathway called transcription-coupled DSB repair (TC-DSBR). Here, using a screening approach scoring multiple outputs in human cells, we identified proteins from the PERIOD complex, ensuring circadian oscillations, as previously unknown TC-DSBR players. We show that PER2 is recruited at TC-DSBs and contributes to their targeting to the nuclear envelope (NE), where SUN1 and the nuclear pore complex (NPC) act as docking sites. TC-DSB anchoring at the NE fosters RAD51 assembly and prevents DSB clustering and translocations. In agreement, the circadian clock regulates TC-DSB targeting to the NE, RAD51 assembly, and DSB clustering. Our study shows a direct link between the circadian rhythm and the response to DSBs in transcribed genes, opening strategies for chrono-chemotherapies based on topoisomerase poisons that induce DSBs in active loci.

Full Text

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Body Clock Proteins Help Repair DNA Damage by Anchoring to the Cell’s Nucleus

Abstract

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