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dc.contributor.authorLeimbacher, P-A
dc.contributor.authorJones, SE
dc.contributor.authorShorrocks, A-MK
dc.contributor.authorde Marco Zompit, M
dc.contributor.authorDay, M
dc.contributor.authorBlaauwendraad, J
dc.contributor.authorBundschuh, D
dc.contributor.authorBonham, S
dc.contributor.authorFischer, R
dc.contributor.authorFink, D
dc.contributor.authorKessler, BM
dc.contributor.authorOliver, AW
dc.contributor.authorPearl, LH
dc.contributor.authorBlackford, AN
dc.contributor.authorStucki, M
dc.date.accessioned2020-08-12T11:09:00Z
dc.date.issued2019-05
dc.identifier.citationMolecular cell, 2019, 74 (3), pp. 571 - 583.e8
dc.identifier.issn1097-2765
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3931
dc.identifier.eissn1097-4164
dc.identifier.doi10.1016/j.molcel.2019.02.014
dc.description.abstractIn mitosis, cells inactivate DNA double-strand break (DSB) repair pathways to preserve genome stability. However, some early signaling events still occur, such as recruitment of the scaffold protein MDC1 to phosphorylated histone H2AX at DSBs. Yet, it remains unclear whether these events are important for maintaining genome stability during mitosis. Here, we identify a highly conserved protein-interaction surface in MDC1 that is phosphorylated by CK2 and recognized by the DNA-damage response mediator protein TOPBP1. Disruption of MDC1-TOPBP1 binding causes a specific loss of TOPBP1 recruitment to DSBs in mitotic but not interphase cells, accompanied by mitotic radiosensitivity, increased micronuclei, and chromosomal instability. Mechanistically, we find that TOPBP1 forms filamentous structures capable of bridging MDC1 foci in mitosis, indicating that MDC1-TOPBP1 complexes tether DSBs until repair is reactivated in the following G1 phase. Thus, we reveal an important, hitherto-unnoticed cooperation between MDC1 and TOPBP1 in maintaining genome stability during cell division.
dc.formatPrint-Electronic
dc.format.extent571 - 583.e8
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.subjectHumans
dc.subjectDNA Damage
dc.subjectChromosomal Instability
dc.subjectGenomic Instability
dc.subjectCarrier Proteins
dc.subjectDNA-Binding Proteins
dc.subjectTrans-Activators
dc.subjectNuclear Proteins
dc.subjectHistones
dc.subjectSignal Transduction
dc.subjectMitosis
dc.subjectG1 Phase
dc.subjectDNA Repair
dc.subjectPhosphorylation
dc.subjectGenome, Human
dc.subjectDNA Breaks, Double-Stranded
dc.titleMDC1 Interacts with TOPBP1 to Maintain Chromosomal Stability during Mitosis.
dc.typeJournal Article
dcterms.dateAccepted2019-02-11
rioxxterms.versionofrecord10.1016/j.molcel.2019.02.014
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
rioxxterms.licenseref.startdate2019-05
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfMolecular cell
pubs.issue3
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.publication-statusPublished
pubs.volume74
pubs.embargo.termsNo embargo
dc.contributor.icrauthorPearl, Laurenceen


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