PERIOD 2 regulates low-dose radioprotection via PER2/pGSK3β/β-catenin/Per2 loop.

Area of Science:

• Radiobiology
• Chronobiology
• Molecular Biology

Background:

• Mammalian cell radiosensitivity exhibits circadian variation.
• Low-level radiation (LDR) can induce adaptive radioprotection.
• The role of clock proteins in LDR-induced radioprotection remains unclear.

Purpose of the Study:

• To investigate the role of Period 2 (PER2) gene in mediating adaptive radioprotection from LDR.
• To elucidate the molecular mechanisms underlying LDR-induced radioprotection involving clock proteins.

Main Methods:

• Comparative analysis of radiosensitivity in wild-type (Per2wt) and Period 2-deficient (Per2def) mice.
• Assessment of DNA repair and mitochondrial function in hematopoietic stem cells and monocytes.
• Investigation of protein interactions and gene transcription pathways in response to LDR in mouse and human cell lines.

Main Results:

• Per2-deficient mice exhibit increased radiosensitivity due to impaired DNA repair and mitochondrial function.
• LDR exposure induces PER2 expression and radioprotection in both mouse and human cells.
• LDR-boosted PER2 interacts with pGSK3β(S9), activating β-catenin and downstream gene transcription involved in DNA repair and mitochondrial function.

Conclusions:

• PER2 is a key mediator of adaptive radioprotection induced by LDR.
• The PER2/pGSK3β/β-catenin/Per2 signaling loop is crucial for LDR-induced radioresistance.
• Targeting this pathway offers potential for protecting normal tissues from radiation damage.