dc.creator | Ceppi, Ilaria | es |
dc.creator | Cannavo, Elda | es |
dc.creator | Bret, Helene | es |
dc.creator | Camarillo Daza, María Rosa | es |
dc.creator | Vivalda, Francesca | es |
dc.creator | Thakur, Roshan Singh | es |
dc.creator | Romero Franco, Amador | es |
dc.creator | Sartori, Alessandro A. | es |
dc.creator | Huertas Sánchez, Pablo | es |
dc.creator | Guerois, Raphael | es |
dc.creator | Cejka, Petr | es |
dc.date.accessioned | 2024-08-01T13:51:40Z | |
dc.date.available | 2024-08-01T13:51:40Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | Ceppi, I., Cannavo, E., Bret, H., Camarillo Daza, M.R., Vivalda, F., Thakur, R.S.,...,Cejka, P. (2023). PLK1 Regulates CtIP and DNA2 Interplay in Long-range DNA end Resection.. Genes & Development, 37 (3-4), 119-135. https://doi.org/10.1101/gad.349981.122. | |
dc.identifier.issn | 1549-5477 | es |
dc.identifier.issn | 0890-9369 | es |
dc.identifier.uri | https://hdl.handle.net/11441/161852 | |
dc.description.abstract | DNA double-strand break (DSB) repair is initiated by DNA end resection. CtIP acts in short-range resection to
stimulate MRE11–RAD50–NBS1 (MRN) to endonucleolytically cleave 5′-terminatedDNAto bypass protein blocks.
CtIP also promotes the DNA2 helicase–nuclease to accelerate long-range resection downstream from MRN. Here,
using AlphaFold2, we identified CtIP-F728E-Y736E as a separation-of-function mutant that is still proficient in
conjunction with MRN but is not able to stimulate ssDNA degradation by DNA2. Accordingly, CtIP-F728E-Y736E
impairs physical interaction with DNA2. Cellular assays revealed that CtIP-F728E-Y736E cells exhibit reduced
DSB-dependent chromatin-bound RPA, impaired long-range resection, and increased sensitivity to DSB-inducing
drugs. Previously, CtIP was shown to be targeted by PLK1 to inhibit long-range resection, yet the underlying
mechanism was unclear. We show that the DNA2-interacting region in CtIP includes the PLK1 target site at S723.
The integrity of S723 in CtIP is necessary for the stimulation of DNA2, and phosphorylation of CtIP by PLK1 in vitro
is consequently inhibitory, explaining why PLK1 restricts long-range resection. Our data support a model in which
CDK-dependent phosphorylation of CtIP activates resection by MRN in S phase, and PLK1-mediated phosphorylation
of CtIP disrupts CtIP stimulation of DNA2 to attenuate long-range resection later at G2/M. | es |
dc.description.sponsorship | European Research Council 681630, 101018257 | es |
dc.description.sponsorship | Swiss National Science Foundation 31003A_175444, 310030_205199, 310030_208143 | es |
dc.description.sponsorship | Ministerio de Ciencia e Innovación PID2019-104195G | es |
dc.description.sponsorship | French government ANR-21-CE44-0009-01 | es |
dc.format | application/pdf | es |
dc.format.extent | 136 p. | es |
dc.language.iso | eng | es |
dc.publisher | Cold Spring Harbor Laboratory Press | es |
dc.relation.ispartof | Genes & Development, 37 (3-4), 119-135. | |
dc.rights | Atribución-NoComercial 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | * |
dc.subject | DNA end resection | es |
dc.subject | DNA repair | es |
dc.subject | Homologous recombination | es |
dc.subject | Phosphorylation | es |
dc.title | PLK1 Regulates CtIP and DNA2 Interplay in Long-range DNA end Resection. | es |
dc.type | info:eu-repo/semantics/article | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Genética | es |
dc.relation.projectID | 681630 | es |
dc.relation.projectID | 101018257 | es |
dc.relation.projectID | 31003A_175444 | es |
dc.relation.projectID | 310030_205199 | es |
dc.relation.projectID | 310030_208143 | es |
dc.relation.projectID | PID2019-104195G | es |
dc.relation.projectID | ANR-21-CE44-0009-01 | es |
dc.relation.publisherversion | https://dx.doi.org/ 10.1101/gad.349981.122 | es |
dc.identifier.doi | 10.1101/gad.349981.122 | es |
dc.journaltitle | Genes & Development | es |
dc.publication.volumen | 37 | es |
dc.publication.issue | 3-4 | es |
dc.publication.initialPage | 119 | es |
dc.publication.endPage | 135 | es |
dc.contributor.funder | European Research Council (ERC) | es |
dc.contributor.funder | Swiss National Science Foundation (SNFS) | es |
dc.contributor.funder | Ministerio de Ciencia e Innovación (MICIN). España | es |
dc.contributor.funder | French government | es |