Publicação
TERRA-mediated recruitment of SMARCAL1 in response to Telomeric Replication Stress
| Resumo: | Telomeres are structures present at the ends of linear eukaryotic chromosomes that are responsible for protecting chromosome ends from being misrecognized as DNA damage, thus avoiding telomere fusions and ensuring genomic stability. Due to their complex nature, telo- meres are difficult to be replicated by the DNA Polymerases and tend to accumulate replication stress that needs to be solved to avoid genomic instability. One of the factors that promotes replication stress at telomeres is the transcription of a telomeric repeat-containing RNA named TERRA. TERRA has a vast range of known functions in both physiological and pathophysiolog- ical conditions in telomere biology and is known to interact with several proteins responsible for diverse functions in the cell. However, the role of many of these interactions remains un- known. SMARCAL1 is a DNA helicase capable of resolving replication stress across the genome and has been shown to interact with TERRA in mouse cell extracts. In this project, we seek to confirm whether SMARCAL1 and TERRA interaction is con- served in human cells and assess how changes in the levels of TERRA transcription and repli- cation stress at telomeres can affect SMARCAL1 localization in the cell. With the results ob- tained, we were able to prove that SMARCAL1 interaction with TERRA is conserved in human cells, particularly human cancer cells. Furthermore, we show how increased TERRA transcrip- tion, as well as high replication stress at telomeres leads to an increase of SMARCAL1 localiza- tion to telomeres, and that this change in SMARCAL1 localization is dependent on its interac- tion with TERRA. Therefore, we show for the first time how TERRA is responsible for the recruit- ment of SMARCAL1 to telomeres in response to telomeric replication stress. |
|---|---|
| Autores principais: | Rebelo, João Pedro Pina |
| Assunto: | SMARCAL1 TERRA Replication Stress ALT Telomeres |
| Ano: | 2023 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| _version_ | 1865920609575239680 |
|---|---|
| author | Rebelo, João Pedro Pina |
| author_facet | Rebelo, João Pedro Pina Rebelo, João Pedro Pina |
| author_role | author |
| contributor_name_str_mv | Azzalin, Claus Baptista, Pedro RUN |
| country_str | PT |
| creators_json_str | [{\"Person.name\":\"Rebelo, João Pedro Pina\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Azzalin, Claus Baptista, Pedro RUN |
| datacite.creators.creator.creatorName.fl_str_mv | Rebelo, João Pedro Pina |
| datacite.date.Accepted.fl_str_mv | 2023-12-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2024-12-04T14:30:44Z |
| datacite.date.embargoed.fl_str_mv | 2024-12-04T14:30:44Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | SMARCAL1 TERRA Replication Stress ALT Telomeres |
| datacite.titles.title.fl_str_mv | TERRA-mediated recruitment of SMARCAL1 in response to Telomeric Replication Stress |
| dc.contributor.none.fl_str_mv | Azzalin, Claus Baptista, Pedro RUN |
| dc.creator.none.fl_str_mv | Rebelo, João Pedro Pina |
| dc.date.Accepted.fl_str_mv | 2023-12-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2024-12-04T14:30:44Z |
| dc.date.embargoed.fl_str_mv | 2024-12-04T14:30:44Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10362/176205 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | SMARCAL1 TERRA Replication Stress ALT Telomeres |
| dc.title.fl_str_mv | TERRA-mediated recruitment of SMARCAL1 in response to Telomeric Replication Stress |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_bdcc |
| description | Telomeres are structures present at the ends of linear eukaryotic chromosomes that are responsible for protecting chromosome ends from being misrecognized as DNA damage, thus avoiding telomere fusions and ensuring genomic stability. Due to their complex nature, telo- meres are difficult to be replicated by the DNA Polymerases and tend to accumulate replication stress that needs to be solved to avoid genomic instability. One of the factors that promotes replication stress at telomeres is the transcription of a telomeric repeat-containing RNA named TERRA. TERRA has a vast range of known functions in both physiological and pathophysiolog- ical conditions in telomere biology and is known to interact with several proteins responsible for diverse functions in the cell. However, the role of many of these interactions remains un- known. SMARCAL1 is a DNA helicase capable of resolving replication stress across the genome and has been shown to interact with TERRA in mouse cell extracts. In this project, we seek to confirm whether SMARCAL1 and TERRA interaction is con- served in human cells and assess how changes in the levels of TERRA transcription and repli- cation stress at telomeres can affect SMARCAL1 localization in the cell. With the results ob- tained, we were able to prove that SMARCAL1 interaction with TERRA is conserved in human cells, particularly human cancer cells. Furthermore, we show how increased TERRA transcrip- tion, as well as high replication stress at telomeres leads to an increase of SMARCAL1 localiza- tion to telomeres, and that this change in SMARCAL1 localization is dependent on its interac- tion with TERRA. Therefore, we show for the first time how TERRA is responsible for the recruit- ment of SMARCAL1 to telomeres in response to telomeric replication stress. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | masterThesis |
| fulltext.url.fl_str_mv | https://run.unl.pt/bitstreams/2028464f-20e1-4390-8749-f0c67ab4133b/download |
| id | run_2b4f3ca52483d97ccaa8e4e769d1fbd4 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10362/176205 |
| instacron_str | unl |
| institution | Universidade Nova de Lisboa |
| instname_str | Universidade Nova de Lisboa |
| language | eng |
| network_acronym_str | run |
| network_name_str | Repositório Institucional da UNL |
| oai_identifier_str | oai:run.unl.pt:10362/176205 |
| organization_str_mv | urn:organizationAcronym:unl |
| person_str_mv | Rebelo, João Pedro Pina |
| publishDate | 2023 |
| reponame_str | Repositório Institucional da UNL |
| repository_id_str | urn:repositoryAcronym:run |
| service_str_mv | urn:repositoryAcronym:run |
| spelling | engpt_PTTelomeres are structures present at the ends of linear eukaryotic chromosomes that are responsible for protecting chromosome ends from being misrecognized as DNA damage, thus avoiding telomere fusions and ensuring genomic stability. Due to their complex nature, telo- meres are difficult to be replicated by the DNA Polymerases and tend to accumulate replication stress that needs to be solved to avoid genomic instability. One of the factors that promotes replication stress at telomeres is the transcription of a telomeric repeat-containing RNA named TERRA. TERRA has a vast range of known functions in both physiological and pathophysiolog- ical conditions in telomere biology and is known to interact with several proteins responsible for diverse functions in the cell. However, the role of many of these interactions remains un- known. SMARCAL1 is a DNA helicase capable of resolving replication stress across the genome and has been shown to interact with TERRA in mouse cell extracts. In this project, we seek to confirm whether SMARCAL1 and TERRA interaction is con- served in human cells and assess how changes in the levels of TERRA transcription and repli- cation stress at telomeres can affect SMARCAL1 localization in the cell. With the results ob- tained, we were able to prove that SMARCAL1 interaction with TERRA is conserved in human cells, particularly human cancer cells. Furthermore, we show how increased TERRA transcrip- tion, as well as high replication stress at telomeres leads to an increase of SMARCAL1 localiza- tion to telomeres, and that this change in SMARCAL1 localization is dependent on its interac- tion with TERRA. Therefore, we show for the first time how TERRA is responsible for the recruit- ment of SMARCAL1 to telomeres in response to telomeric replication stress.application/pdfpt_PTTERRA-mediated recruitment of SMARCAL1 in response to Telomeric Replication StressRebelo, João Pedro PinaAzzalin, ClausBaptista, PedroHostingInstitutionOrganizationalRUNe-mailmailto:run@unl.ptrun@unl.pt2024-12-04T14:30:44Z2023-122023-12-01T00:00:00ZHandlehttp://hdl.handle.net/10362/176205http://purl.org/coar/access_right/c_abf2open accessSMARCAL1TERRAReplication StressALTTelomeres1723026 bytesliteraturehttp://purl.org/coar/resource_type/c_bdccmaster thesishttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://run.unl.pt/bitstreams/2028464f-20e1-4390-8749-f0c67ab4133b/download |
| spellingShingle | TERRA-mediated recruitment of SMARCAL1 in response to Telomeric Replication Stress TERRA-mediated recruitment of SMARCAL1 in response to Telomeric Replication Stress Rebelo, João Pedro Pina SMARCAL1 TERRA Replication Stress ALT Telomeres Rebelo, João Pedro Pina SMARCAL1 TERRA Replication Stress ALT Telomeres |
| status | NEW |
| subject.fl_str_mv | SMARCAL1 TERRA Replication Stress ALT Telomeres |
| title | TERRA-mediated recruitment of SMARCAL1 in response to Telomeric Replication Stress |
| title_full | TERRA-mediated recruitment of SMARCAL1 in response to Telomeric Replication Stress |
| title_fullStr | TERRA-mediated recruitment of SMARCAL1 in response to Telomeric Replication Stress TERRA-mediated recruitment of SMARCAL1 in response to Telomeric Replication Stress |
| title_full_unstemmed | TERRA-mediated recruitment of SMARCAL1 in response to Telomeric Replication Stress TERRA-mediated recruitment of SMARCAL1 in response to Telomeric Replication Stress |
| title_short | TERRA-mediated recruitment of SMARCAL1 in response to Telomeric Replication Stress |
| title_sort | TERRA-mediated recruitment of SMARCAL1 in response to Telomeric Replication Stress |
| topic | SMARCAL1 TERRA Replication Stress ALT Telomeres |
| topic_facet | SMARCAL1 TERRA Replication Stress ALT Telomeres |
| url | http://hdl.handle.net/10362/176205 |
| visible | 1 |