dc.contributor.author | Fletcher, SC | |
dc.contributor.author | Grou, CP | |
dc.contributor.author | Legrand, AJ | |
dc.contributor.author | Chen, X | |
dc.contributor.author | Soderstrom, K | |
dc.contributor.author | Poletto, M | |
dc.contributor.author | Dianov, GL | |
dc.date.accessioned | 2018-03-27T10:51:32Z | |
dc.date.issued | 2018-02-28 | |
dc.identifier.citation | Nucleic acids research, 2018, 46 (4), pp. 1834 - 1846 | |
dc.identifier.issn | 0305-1048 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1613 | |
dc.identifier.eissn | 1362-4962 | |
dc.identifier.doi | 10.1093/nar/gkx1291 | |
dc.description.abstract | ATM (ataxia-telangiectasia mutated) is a central molecule for DNA quality control. Its activation by DNA damage promotes cell-cycle delay, which facilitates DNA repair prior to replication. On the other hand, persistent DNA damage has been implicated in ATM-dependent cell death via apoptosis; however, the mechanisms underlying this process remain elusive. Here we find that, in response to persistent DNA strand breaks, ATM phosphorylates transcription factor Sp1 and initiates its degradation. We show that Sp1 controls expression of the key base excision repair gene XRCC1, essential for DNA strand break repair. Therefore, degradation of Sp1 leads to a vicious cycle that involves suppression of DNA repair and further aggravation of the load of DNA damage. This activates transcription of pro-apoptotic genes and renders cells susceptible to elimination via both apoptosis and natural killer cells. These findings constitute a previously unrecognized 'gatekeeper' function of ATM as a detector of cells with persistent DNA damage. | |
dc.format | Print | |
dc.format.extent | 1834 - 1846 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | OXFORD UNIV PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Killer Cells, Natural | |
dc.subject | Cells, Cultured | |
dc.subject | Humans | |
dc.subject | DNA Damage | |
dc.subject | Serine | |
dc.subject | Apoptosis | |
dc.subject | DNA Repair | |
dc.subject | Down-Regulation | |
dc.subject | Phosphorylation | |
dc.subject | Male | |
dc.subject | Sp1 Transcription Factor | |
dc.subject | Ataxia Telangiectasia Mutated Proteins | |
dc.subject | X-ray Repair Cross Complementing Protein 1 | |
dc.title | Sp1 phosphorylation by ATM downregulates BER and promotes cell elimination in response to persistent DNA damage. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-12-19 | |
rioxxterms.versionofrecord | 10.1093/nar/gkx1291 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-02 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nucleic acids research | |
pubs.issue | 4 | |
pubs.notes | Not known | |
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/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Cell Death and Immunity | |
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/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Cell Death and Immunity | |
pubs.publication-status | Published | |
pubs.volume | 46 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cell Death and Immunity | |
dc.contributor.icrauthor | Legrand, Arnaud | |