Author ORCiD
Date of Award
2026
Document Type
Thesis
Degree Name
Doctor of Philosophy (PhD)
Thesis Advisor
Titia de Lange
Keywords
KU70/80, DNA repair, ribosome biogenesis, essential function, primate specific, ribosomal RNA
Abstract
The requirement of Ku70/80 for ribosome biogenesis in higher primates explains otherwise perplexing essential nature of this double-strand break (DSB) repair factor. We have ruled out telomere protection or DSB repair as the essential function ofKu70/80. Instead, unbiased genome-wide analyses pointed to a role in ribosome biogenesis. Human Ku70/80, but not mouse Ku70/80 is enriched in the nucleolus at the Dense Fibrillar Component (DFC) periphery, likely via co-evolved protein-protein interactions with nucleolar factors. Consistent with its localization in the nucleolus, human Ku70/80 null cells exhibit ribosomal RNA (rRNA) processing defect and consequent shutdown of protein synthesis offer a direct explanation for cell viability loss. Through a series of complementary experiments, we also show that it is human Ku80that is required for Ku70/80 nucleolar function. Together, these data support a model in which Ku70/80 has acquired a second, species-specific function in ribosome biogenesis, accounting for its essential nature in higher primates. Future work will be required to identify the nucleolar factors involved and determine the mechanism by whichKu70/80 contributes to rRNA maturation.
License and Reuse Information
This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.
Recommended Citation
Zakusilo, George, "Investigations into Why Human (but not mouse) KU70/80 is Essential Reveal a Role for Human KU70/80 in Ribosome Biogenesis" (2026). Student Theses and Dissertations. 848.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/848
Comments
A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy