dc.contributor.author | Sonmez, C | |
dc.contributor.author | Toia, B | |
dc.contributor.author | Eickhoff, P | |
dc.contributor.author | Matei, AM | |
dc.contributor.author | El Beyrouthy, M | |
dc.contributor.author | Wallner, B | |
dc.contributor.author | Douglas, ME | |
dc.contributor.author | de Lange, T | |
dc.contributor.author | Lottersberger, F | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2024-05-20T11:24:25Z | |
dc.date.available | 2024-05-20T11:24:25Z | |
dc.date.issued | 2024-05-08 | |
dc.identifier | 7614134 | |
dc.identifier.citation | Nucleic Acids Research (NAR), 2024, 52 (8), pp. 4313 - 4327 | |
dc.identifier.issn | 0305-1048 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6237 | |
dc.identifier.eissn | 1362-4962 | |
dc.identifier.eissn | 1362-4962 | |
dc.identifier.doi | 10.1093/nar/gkae105 | |
dc.identifier.doi | 10.1093/nar/gkae105 | |
dc.description.abstract | The complex formed by Ku70/80 and DNA-PKcs (DNA-PK) promotes the synapsis and the joining of double strand breaks (DSBs) during canonical non-homologous end joining (c-NHEJ). In c-NHEJ during V(D)J recombination, DNA-PK promotes the processing of the ends and the opening of the DNA hairpins by recruiting and/or activating the nuclease Artemis/DCLRE1C/SNM1C. Paradoxically, DNA-PK is also required to prevent the fusions of newly replicated leading-end telomeres. Here, we describe the role for DNA-PK in controlling Apollo/DCLRE1B/SNM1B, the nuclease that resects leading-end telomeres. We show that the telomeric function of Apollo requires DNA-PKcs's kinase activity and the binding of Apollo to DNA-PK. Furthermore, AlphaFold-Multimer predicts that Apollo's nuclease domain has extensive additional interactions with DNA-PKcs, and comparison to the cryo-EM structure of Artemis bound to DNA-PK phosphorylated on the ABCDE/Thr2609 cluster suggests that DNA-PK can similarly grant Apollo access to the DNA end. In agreement, the telomeric function of DNA-PK requires the ABCDE/Thr2609 cluster. These data reveal that resection of leading-end telomeres is regulated by DNA-PK through its binding to Apollo and its (auto)phosphorylation-dependent positioning of Apollo at the DNA end, analogous but not identical to DNA-PK dependent regulation of Artemis at hairpins. | |
dc.format | Print | |
dc.format.extent | 4313 - 4327 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | OXFORD UNIV PRESS | |
dc.relation.ispartof | Nucleic Acids Research (NAR) | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | DNA-Activated Protein Kinase | |
dc.subject | Telomere | |
dc.subject | Humans | |
dc.subject | DNA-Binding Proteins | |
dc.subject | Endonucleases | |
dc.subject | DNA End-Joining Repair | |
dc.subject | Nuclear Proteins | |
dc.subject | Ku Autoantigen | |
dc.subject | Protein Binding | |
dc.subject | DNA Breaks, Double-Stranded | |
dc.subject | Phosphorylation | |
dc.subject | DNA | |
dc.title | DNA-PK controls Apollo's access to leading-end telomeres. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2024-02-01 | |
dc.date.updated | 2024-05-20T11:23:54Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1093/nar/gkae105 | |
rioxxterms.licenseref.startdate | 2024-05-08 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/38407308 | |
pubs.issue | 8 | |
pubs.organisational-group | ICR | |
pubs.organisational-group | ICR/Primary Group | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Cancer Biology/Telomere Biology | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1093/nar/gkae105 | |
pubs.volume | 52 | |
icr.researchteam | Telomere Biology | |
dc.contributor.icrauthor | Douglas, Maxwell | |
icr.provenance | Deposited by Mr Arek Surman (impersonating Prof Ros Eeles) on 2024-05-20. Deposit type is initial. No. of files: 1. Files: gkae105.pdf | |