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.
","abstract_html":"<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>","abstract_has_math":false,"creators":["Zakusilo, George"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Titia de Lange"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2026,"date_issued":"2026-01-01T08:00:00Z","date_published":"2026-01-01T08:00:00Z","updated_at":"2026-07-24T04:11:55Z","subjects":["KU70/80","DNA repair","ribosome biogenesis","essential function","primate specific","ribosomal RNA","Life Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/848","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Titia de Lange"]},{"key":"dc:creator","label":"Author","values":["Zakusilo, George"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2026-10-14T07:00:00Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["KU70/80","DNA repair","ribosome biogenesis","essential function","primate specific","ribosomal RNA","Life Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/848"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:title","label":"Title","values":["Investigations into Why Human (but not mouse) KU70/80 is Essential Reveal a Role for Human KU70/80 in Ribosome Biogenesis"]}]}],"canonical_facts":{"dc:contributor":["Titia de Lange"],"dc:creator":["Zakusilo, George"],"dc:date.available":["2026-10-14T07:00:00Z"],"dc:description.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.
"],"dc:identifier":["https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/848"],"dc:subject":["KU70/80","DNA repair","ribosome biogenesis","essential function","primate specific","ribosomal RNA","Life Sciences"],"dc:title":["Investigations into Why Human (but not mouse) KU70/80 is Essential Reveal a Role for Human KU70/80 in Ribosome Biogenesis"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T04:11:55Z"}