Treacle-dependent TOPBP1 condensation regulates the nucleolar DNA damage response - PubMed
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- #ribosomal DNA repair
- #phase separation
- #DNA damage response
- Treacle facilitates phase separation of TOPBP1 in the nucleolus's fibrillar centers, creating a localized platform for DDR signaling.
- Phosphorylation of Treacle by CK2 and ATR/ATM enables it to interact with TOPBP1, nucleating condensation to enhance ATR/ATM activation and γH2AX signaling.
- Treacle-dependent condensation directs DNA repair toward homologous recombination; its disruption shifts repair to DNA-PK-dependent nonhomologous end-joining, leading to faster early repair but incomplete long-term resolution.
- This mechanism ensures accurate maintenance and stability of highly repetitive ribosomal DNA arrays by coordinating the nucleolar DNA damage response.