Investigations into Why Human (but not mouse) KU70/80 is Essential Reveal a Role for Human KU70/80 in Ribosome Biogenesis

<p>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.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Thesis

Year dc:date.available

2026

Author dc:creator

• Zakusilo, George

Contributors dc:contributor

• Titia de Lange

• KU70/80
• DNA repair
• ribosome biogenesis
• essential function
• primate specific
• ribosomal RNA
• Life Sciences

Repository record dc:identifier

https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/848

OAI identifier oai:identifier

oai:digitalcommons.rockefeller.edu:student_theses_and_dissertations-1852