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bioRxiv · 10.64898/2026.09.01.748474

A Sequential Assembly Mechanism for Stable Cdc13 Dimerization on Telomeric DNA

Chiu, P.-W.·Lin, Y.-T.·Lai, P.-R.·Lee, T.-Y.·Cheng, Y.-C.·Hsieh, Y.-Z.·Li, H.-W.·Lin, J.-J.
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Abstract

The telomere-binding protein Cdc13 specifically binds to single-stranded telomeric DNA, playing a critical role in telomere protection and length regulation. While extensive biochemical, molecular biological, and genetic studies have shown that Cdc13 can form dimers or oligomers in solution and bind telomeric DNA with high specificity, the dynamic mechanism of its loading onto telomeres is less well characterized. Using two single-molecule methods, single-molecule fluorescence resonance energy transfer (smFRET) and colocalization single-molecule spectroscopy (CoSMoS), we demonstrate that Cdc13 initially loads onto telomeres as a monomer. This is followed by the recruitment of a second monomer, forming a stable Cdc13 dimer on a 12-nucleotide telomeric DNA segment. Although genetic studies suggest that monomeric Cdc13 binding alone is insufficient to maintain telomere length, it underscores the Cdc13 monomers regulatory importance in coordinating telomere synthesis and protection. This monomer-to-dimer transition provides a mechanistic basis for understanding the multi-tasked roles of Cdc13 in telomere replication and protection.

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Chiu, P.-W., Lin, Y.-T., Lai, P.-R., Lee, T.-Y., Cheng, Y.-C., Hsieh, Y.-Z., Li, H.-W., Lin, J.-J.. 2026-09-02. A Sequential Assembly Mechanism for Stable Cdc13 Dimerization on Telomeric DNA. https://doi.org/10.64898/2026.09.01.748474

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