Replication stress links Geminin depletion to centrosome amplification

Geminin depletion in proliferating mouse embryonic fibroblasts induces robust centrosome amplification alongside impaired primary cilium assembly, linked to replication stress and ATR-dependent signaling.

• Why it matters: Defects in DNA replication licensing are known to disrupt genome duplication, but how they are coupled to centrosome homeostasis is unclear.
• What they did: The study depleted Geminin in mouse embryonic fibroblasts and assessed centrosome amplification, primary cilium assembly, DNA damage across the cell cycle, and activation of an ATR-dependent DNA damage response.
• The result: Replication stress from Geminin loss activated the ATR–Chk1–Wee1 checkpoint axis, prolonged G2, and led to premature centriole disengagement, enabling centrosome amplification.

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