TY  - JOUR
AU  - Mamar, Hasan
AU  - Fajka-Boja, Roberta
AU  - Mórocz, Mónika
AU  - Pinto, Eva
AU  - Zentout, Siham
AU  - Mihut, Alexandra
AU  - Kopasz, Anna Georgina
AU  - Mérey, Mihály
AU  - Smith, Rebecca
AU  - Haracska, Lajos
AU  - Huet, Sébastien
AU  - Timinszky, Gyula
TI  - The loss of DNA polymerase epsilon accessory subunits POLE3-POLE4 leads to BRCA1-independent PARP inhibitor sensitivity
JF  - NUCLEIC ACIDS RESEARCH
J2  - NUCLEIC ACIDS RES
VL  - 52
PY  - 2024
IS  - 12
SP  - 6994
EP  - 7011
PG  - 18
SN  - 0305-1048
DO  - 10.1093/nar/gkae439
UR  - https://m2.mtmt.hu/api/publication/34169536
ID  - 34169536
AB  - The clinical success of PARP1/2 inhibitors (PARPi) prompts the expansion of their applicability beyond homologous recombination deficiency. Here, we demonstrate that the loss of the accessory subunits of DNA polymerase epsilon, POLE3 and POLE4, sensitizes cells to PARPi. We show that the sensitivity of POLE4 knockouts is not due to compromised response to DNA damage or homologous recombination deficiency. Instead, POLE4 loss affects replication speed leading to the accumulation of single-stranded DNA gaps behind replication forks upon PARPi treatment, due to impaired post-replicative repair. POLE4 knockouts elicit elevated replication stress signaling involving ATR and DNA-PK. We find POLE4 to act parallel to BRCA1 in inducing sensitivity to PARPi and counteracts acquired resistance associated with restoration of homologous recombination. Altogether, our findings establish POLE4 as a promising target to improve PARPi driven therapies and hamper acquired PARPi resistance.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Juhász, Szilvia
AU  - Smith, Rebecca
AU  - Schauer, Tamás
AU  - Spekhardt, Dóra
AU  - Mamar, Hasan
AU  - Zentout, Siham
AU  - Chapuis, Catherine
AU  - Huet, Sébastien
AU  - Timinszky, Gyula
TI  - The chromatin remodeler ALC1 underlies resistance to PARP inhibitor treatment
JF  - SCIENCE ADVANCES
J2  - SCI ADV
VL  - 6
PY  - 2020
IS  - 51
SN  - 2375-2548
DO  - 10.1126/sciadv.abb8626
UR  - https://m2.mtmt.hu/api/publication/31798190
ID  - 31798190
N1  - MTA SZBK Lendület DNA Damage and Nuclear Dynamics Research Group, Institute of Genetics, Biological Research Centre, Szeged, 6276, Hungary            
            Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes), UMR 6290, BIOSIT, UMS 3480, Rennes, F-35000, France            
            Biomedical Center, Bioinformatics Unit, Ludwig Maximilian University of Munich, Planegg-Martinsried, 82152, Germany            
            Institut Universitaire de France, Paris, France            
            Cited By :1            
            Export Date: 17 February 2021            
            Correspondence Address: Huet, S.; Univ Rennes, France; email: sebastien.huet@univ-rennes1.fr            
            Correspondence Address: Timinszky, G.; MTA SZBK Lendület DNA Damage and Nuclear Dynamics Research Group, Hungary; email: timinszky.gyula@brc.hu
MTA SZBK Lendület DNA Damage and Nuclear Dynamics Research Group, Institute of Genetics, Biological Research Centre, Szeged, 6276, Hungary            
            Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes), UMR 6290, BIOSIT, UMS 3480, Rennes, F-35000, France            
            Biomedical Center, Bioinformatics Unit, Ludwig Maximilian University of Munich, Planegg-Martinsried, 82152, Germany            
            Institut Universitaire de France, Paris, France            
            Cited By :3            
            Export Date: 22 April 2021            
            Correspondence Address: Huet, S.; Univ Rennes, France; email: sebastien.huet@univ-rennes1.fr            
            Correspondence Address: Timinszky, G.; MTA SZBK Lendület DNA Damage and Nuclear Dynamics Research Group, Hungary; email: timinszky.gyula@brc.hu
MTA SZBK Lendület DNA Damage and Nuclear Dynamics Research Group, Institute of Genetics, Biological Research Centre, Szeged, 6276, Hungary            
            Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes), UMR 6290, BIOSIT, UMS 3480, Rennes, F-35000, France            
            Biomedical Center, Bioinformatics Unit, Ludwig Maximilian University of Munich, Planegg-Martinsried, 82152, Germany            
            Institut Universitaire de France, Paris, France            
            Cited By :3            
            Export Date: 7 May 2021            
            Correspondence Address: Huet, S.; Univ Rennes, France; email: sebastien.huet@univ-rennes1.fr            
            Correspondence Address: Timinszky, G.; MTA SZBK Lendület DNA Damage and Nuclear Dynamics Research Group, Hungary; email: timinszky.gyula@brc.hu
LA  - English
DB  - MTMT
ER  -