{"id":{"repo_id":"cambridge","oai_identifier":"oai:www.repository.cam.ac.uk:1810/371353"},"canonical_url":"https://search.dev.ndltd.org/etd/cambridge/oai:www.repository.cam.ac.uk:1810/371353","repository":{"repo_id":"cambridge","name":"Cambridge University","base_url":"https://api.repository.cam.ac.uk/server/oai/request"},"display":{"title":"Origins of non-coding Y RNA family and its role in DNA replication","abstract":"Y RNAs are a family of non-coding RNAs that are required for chromosomal DNA replication initiation in vertebrates. Specifically, Y RNAs play an essential role in the establishment of new DNA replication forks during G1 to S phase transition. However, the mechanism by which Y RNAs contribute to initiation of DNA replication, as well as the evolution of Y RNAs through vertebrates and invertebrates remain unknown. Y RNA upper stem domain is a minimum essential domain that conveys the Y RNA replication initiation activity. Here, I have established a single nucleotide contribution to the DNA replication activity of the upper stem domain. I have showed that the upper stem length, specific bases of its 5’-GUG-CAC-3’ motif and orientation of its G:C clamp motifs must be rigidly conserved for the DNA replication initiation activity to be preserved. Furthermore, I showed that replication factors such as ORC, Cdc6 and Cdt1 are unlikely to interact with the Y RNA upper stem domain, contrary to previous findings. Functional homologs of Y RNAs called sbRNAs, have been identified in the nematode genus *Caenorhabditis*. However, no additional Y RNAs were found in direct vertebrate ancestors, nor in any other invertebrate species. I analysed two distant invertebrate genera: the insect *Drosophila* group and a direct vertebrate ancestor, a chordate subphylum, lancelets. I demonstrated that previously established *Drosophila* Y RNA candidates do not initiate DNA replication despite possessing the upper stem domain and are in fact not part of the Y RNA family. Additionally, I successfully identified novel group of invertebrate Y RNAs in lancelets which demonstrated DNA replication initiation activity as well as high levels of expression in endogenous organisms. Therefore, in this thesis, I have further clarified the role of Y RNAs during DNA replication as well as identified ancestral Y RNAs showing that they are more prevalent during pre-vertebrate evolution than previously thought.","abstract_html":"Y RNAs are a family of non-coding RNAs that are required for chromosomal DNA replication initiation in vertebrates. Specifically, Y RNAs play an essential role in the establishment of new DNA replication forks during G1 to S phase transition. However, the mechanism by which Y RNAs contribute to initiation of DNA replication, as well as the evolution of Y RNAs through vertebrates and invertebrates remain unknown. Y RNA upper stem domain is a minimum essential domain that conveys the Y RNA replication initiation activity. Here, I have established a single nucleotide contribution to the DNA replication activity of the upper stem domain. I have showed that the upper stem length, specific bases of its 5’-GUG-CAC-3’ motif and orientation of its G:C clamp motifs must be rigidly conserved for the DNA replication initiation activity to be preserved. Furthermore, I showed that replication factors such as ORC, Cdc6 and Cdt1 are unlikely to interact with the Y RNA upper stem domain, contrary to previous findings. Functional homologs of Y RNAs called sbRNAs, have been identified in the nematode genus *Caenorhabditis*. However, no additional Y RNAs were found in direct vertebrate ancestors, nor in any other invertebrate species. I analysed two distant invertebrate genera: the insect *Drosophila* group and a direct vertebrate ancestor, a chordate subphylum, lancelets. I demonstrated that previously established *Drosophila* Y RNA candidates do not initiate DNA replication despite possessing the upper stem domain and are in fact not part of the Y RNA family. Additionally, I successfully identified novel group of invertebrate Y RNAs in lancelets which demonstrated DNA replication initiation activity as well as high levels of expression in endogenous organisms. Therefore, in this thesis, I have further clarified the role of Y RNAs during DNA replication as well as identified ancestral Y RNAs showing that they are more prevalent during pre-vertebrate evolution than previously thought.","abstract_has_math":false,"creators":["Pavlickova, Milena"],"institution":"University of Cambridge","degree_name":"Doctor of Philosophy (PhD)","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Krude, Torsten"],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021-12-28","date_published":"2021-12-28","updated_at":"2026-07-22T22:24:17Z","subjects":["DNA replication","DNA replication origin","lancelet","non-coding RNAs","sbRNA","vertebrate DNA replication","Y RNA"],"languages":["eng"],"rights":[],"rights_urls":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/2945bde0-bb08-4f78-b21d-7d90386474a1/download","https://www.rioxx.net/licenses/all-rights-reserved/"],"identifier_entries":[]},"links":{"outbound_url":"https://doi.org/10.17863/CAM.110562","outbound_label":"DOI","outbound_source":"dc:identifier.doi"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Krude, Torsten"]},{"key":"dc:creator","label":"Author","values":["Pavlickova, Milena"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2021-12-28"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Cambridge"]},{"key":"dc:relation.isreferencedby.uri","label":"Dc Relation Isreferencedby URI","values":["https://www.repository.cam.ac.uk/handle/1810/371353"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["DNA replication","DNA replication origin","lancelet","non-coding RNAs","sbRNA","vertebrate DNA replication","Y RNA"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/2945bde0-bb08-4f78-b21d-7d90386474a1/download","https://www.rioxx.net/licenses/all-rights-reserved/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.17863/CAM.110562"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/a3b047c4-4a7f-4cc0-9155-5d200072c671/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Y RNAs are a family of non-coding RNAs that are required for chromosomal DNA replication initiation in vertebrates. 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Functional homologs of Y RNAs called sbRNAs, have been identified in the nematode genus *Caenorhabditis*. However, no additional Y RNAs were found in direct vertebrate ancestors, nor in any other invertebrate species. I analysed two distant invertebrate genera: the insect *Drosophila* group and a direct vertebrate ancestor, a chordate subphylum, lancelets. I demonstrated that previously established *Drosophila* Y RNA candidates do not initiate DNA replication despite possessing the upper stem domain and are in fact not part of the Y RNA family. Additionally, I successfully identified novel group of invertebrate Y RNAs in lancelets which demonstrated DNA replication initiation activity as well as high levels of expression in endogenous organisms. 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