RT info:eu-repo/semantics/article
T1 PHF2 regulates homology-directed DNA repair by controlling the resection of DNA double strand breaks
A1 Hernández Fernaud, Juan Ramón
A1 Alonso de Vega, Ignacio
A1 Paz Cabrera, María Cristina
A1 Rother, Magdalena B.
A1 Wiegant, Wouter W.
A1 Checa Rodr´ıguez, Cintia
A1 Huertas, Pablo
A1 Freire, Raimundo
A1 Attikum, Haico van
A1 Smits, Veronique A..J.
A2 BioquímicaMicrobiología, Biología Celular y Genética
A2 Unidad de InvestigaciónHospital Universitario de Canarias.
AB Post-translational histone modifications and chromatinremodelling play a critical role controlling theintegrity of the genome. Here, we identify histone lysinedemethylase PHF2 as a novel regulator of theDNA damage response by regulating DNA damageinducedfocus formation of 53BP1 and BRCA1, criticalfactors in the pathway choice for DNA doublestrand break repair. PHF2 knockdown leads to impairedBRCA1 focus formation and delays the resolutionof 53BP1 foci. Moreover, irradiation-inducedRPA phosphorylation and focus formation, as wellas localization of CtIP, required for DNA end resection,to sites of DNA lesions are affected by depletionof PHF2. These results are indicative of a defectiveresection of double strand breaks and therebyan impaired homologous recombination upon PHF2depletion. In accordance with these data, Rad51 focusformation and homology-directed double strandbreak repair is inhibited in cells depleted for PHF2.Importantly, we demonstrate that PHF2 knockdowndecreases CtIP and BRCA1 protein and mRNA levels,an effect that is dependent on the demethylaseactivity of PHF2. Furthermore, PHF2-depleted cellsdisplay genome instability and aremildly sensitive tothe inhibition of PARP. Together these results demonstratethat PHF2 promotes DNA repair by homologousrecombination by controlling CtIP-dependentresection of double strand breaks.
YR 2020
FD 2020
LK http://riull.ull.es/xmlui/handle/915/38840
UL http://riull.ull.es/xmlui/handle/915/38840
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DS Repositorio institucional de la Universidad de La Laguna
RD 19-oct-2024