TY - JOUR AU - Paeschke, Katrin AU - Burkovics, Péter TI - Mgs1 function at G-quadruplex structures during DNA replication JF - CURRENT GENETICS J2 - CURR GENET VL - 67 PY - 2021 IS - 2 SP - 225 EP - 230 PG - 6 SN - 0172-8083 DO - 10.1007/s00294-020-01128-1 UR - https://m2.mtmt.hu/api/publication/31780806 ID - 31780806 N1 - Cited By :2 Export Date: 11 July 2022 CODEN: CUGED AB - The coordinated action of DNA polymerases and DNA helicases is essential at genomic sites that are hard to replicate. Among these are sites that harbour G-quadruplex DNA structures (G4). G4s are stable alternative DNA structures, which have been implicated to be involved in important cellular processes like the regulation of gene expression or telomere maintenance. G4 structures were shown to hinder replication fork progression and cause genomic deletions, mutations and recombination events. Many helicases unwind G4 structures and preserve genome stability, but a detailed understanding of G4 replication and the re-start of stalled replication forks around formed G4 structures is not clear, yet. In our recent study, we identified that Mgs1 preferentially binds to G4 DNA structures in vitro and is associated with putative G4-forming chromosomal regions in vivo. Mgs1 binding to G4 motifs in vivo is partially dependent on the helicase Pif1. Pif1 is the major G4-unwinding helicase in S. cerevisiae. In the absence of Mgs1, we determined elevated gross chromosomal rearrangement (GCR) rates in yeast, similar to Pif1 deletion. Here, we highlight the recent findings and set these into context with a new mechanistic model. We propose that Mgs1's functions support DNA replication at G4-forming regions. LA - English DB - MTMT ER - TY - JOUR AU - Zacheja, Theresa AU - Tóth, Ágnes AU - Harami, Gábor AU - Yang, Qianlu AU - Schwindt, Eike AU - Kovács, Mihály AU - Paeschke, Katrin AU - Burkovics, Péter TI - Mgs1 protein supports genome stability via recognition of G-quadruplex DNA structures JF - FASEB JOURNAL J2 - FASEB J VL - 34 PY - 2020 IS - 9 SP - 12646 EP - 12662 PG - 17 SN - 0892-6638 DO - 10.1096/fj.202000886R UR - https://m2.mtmt.hu/api/publication/31397391 ID - 31397391 N1 - WoS:hiba:000558208300001 2020-09-01 18:01 folyóirat nem egyezik LA - English DB - MTMT ER - TY - CHAP AU - Almási, Karola AU - Burkovics, Péter ED - Buday, László ED - Erdélyi, Miklós ED - Kovács, Mihály ED - Mihály, József ED - Varga, Máté ED - Virág, László ED - Hohol, Róbert TI - Analysis of the function of Saccharomyces cerevisiae Mgs1 protein in G-quadruplex replication T2 - Hungarian Molecular Life Sciences 2019: Programme and Books of abstracts PB - Diamond Congress Kft. CY - Budapest SN - 9786155270529 PY - 2019 SP - 254 EP - 255 PG - 2 UR - https://m2.mtmt.hu/api/publication/32867359 ID - 32867359 LA - English DB - MTMT ER - TY - JOUR AU - Smith, Rebecca AU - Lebeaupin, Théo AU - Juhász, Szilvia AU - Chapuis, Catherine AU - D'Augustin, Ostiane AU - Dutertre, Stéphanie AU - Burkovics, Péter AU - Biertuempfel, Christian AU - Timinszky, Gyula AU - Huet, Sébastien TI - Poly(ADP-ribose)-dependent chromatin unfolding facilitates the association of DNA-binding proteins with DNA at sites of damage JF - NUCLEIC ACIDS RESEARCH J2 - NUCLEIC ACIDS RES VL - 47 PY - 2019 IS - 21 SP - 11250 EP - 11267 PG - 18 SN - 0305-1048 DO - 10.1093/nar/gkz820 UR - https://m2.mtmt.hu/api/publication/30807243 ID - 30807243 N1 - Cited By :1 Export Date: 9 December 2019 LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Ágnes AU - Hegedűs, Lili AU - Juhász, Szilvia AU - Haracska, Lajos AU - Burkovics, Péter TI - The DNA-binding box of human SPARTAN contributes to the targeting of Poleta to DNA damage sites. JF - DNA REPAIR J2 - DNA REPAIR VL - 49 PY - 2017 SP - 33 EP - 42 PG - 10 SN - 1568-7864 DO - 10.1016/j.dnarep.2016.10.007 UR - https://m2.mtmt.hu/api/publication/3140736 ID - 3140736 AB - Inappropriate repair of UV-induced DNA damage results in human diseases such as Xeroderma pigmentosum (XP), which is associated with an extremely high risk of skin cancer. A variant form of XP is caused by the absence of Poleta, which is normally able to bypass UV-induced DNA lesions in an error-free manner. However, Poleta is highly error prone when replicating undamaged DNA and, thus, the regulation of the proper targeting of Poleta is crucial for the prevention of mutagenesis and UV-induced cancer formation. Spartan is a novel regulator of the damage tolerance pathway, and its association with Ub-PCNA has a role in Poleta targeting; however, our knowledge about its function is only rudimentary. Here, we describe a new biochemical property of purified human SPARTAN by showing that it is a DNA-binding protein. Using a DNA binding mutant, we provide in vivo evidence that DNA binding by SPARTAN regulates the targeting of Poleta to damage sites after UV exposure, and this function contributes highly to its DNA-damage tolerance function. LA - English DB - MTMT ER - TY - JOUR AU - Burkovics, Péter AU - Hegedűs, Lili AU - Juhász, Szilvia AU - Altmannova, V AU - Sebesta, M AU - Pacesa, M AU - Fugger, K AU - Sorensen, CS AU - Lee, MY AU - Haracska, Lajos AU - Krejci, L TI - The PCNA-associated protein PARI negatively regulates homologous recombination via the inhibition of DNA repair synthesis. JF - NUCLEIC ACIDS RESEARCH J2 - NUCLEIC ACIDS RES VL - 44 PY - 2016 IS - 7 SP - 3176 EP - 3189 PG - 14 SN - 0305-1048 DO - 10.1093/nar/gkw024 UR - https://m2.mtmt.hu/api/publication/3028656 ID - 3028656 N1 - Megjegyzés-25820712 N1 Funding Details: GACR, Czech Science Foundation Megjegyzés-25820723 N1 Funding Details: GACR, Czech Science Foundation Megjegyzés-25820765 N1 Funding Details: GACR, Czech Science Foundation Megjegyzés-25820780 N1 Funding Details: GACR, Czech Science Foundation Megjegyzés-25820798 N1 Funding Details: GACR, Czech Science Foundation Megjegyzés-25820812 N1 Funding Details: GACR, Czech Science Foundation Megjegyzés-25820825 N1 Funding Details: GACR, Czech Science Foundation Megjegyzés-25820833 N1 Funding Details: GACR, Czech Science Foundation Megjegyzés-25820836 N1 Funding Details: GACR, Czech Science Foundation Megjegyzés-25820840 N1 Funding Details: GACR, Czech Science Foundation Megjegyzés-25820849 N1 Funding Details: GACR, Czech Science Foundation Megjegyzés-25820852 N1 Funding Details: GACR, Czech Science Foundation Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged, 6726, Hungary Department of Biology, Masaryk University, Brno, 62500, Czech Republic National Centre for Biomolecular Research, Masaryk University, Brno, 62500, Czech Republic International Clinical Research Center, Center for Biomolecular and Cellular Engineering, St Anne's University, Brno, 65691, Czech Republic Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, 2200, Denmark Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, United States Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX13RE, United Kingdom Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, Zurich, CH-8057, Switzerland Francis Crick Institute, Clare Hall Laboratory, South Mimms, EN63LD, United Kingdom Cited By :23 Export Date: 11 May 2021 CODEN: NARHA Correspondence Address: Burkovics, P.; Institute of Genetics, Hungary; email: burkovics.peter@brc.mta.hu AB - Successful and accurate completion of the replication of damage-containing DNA requires mainly recombination and RAD18-dependent DNA damage tolerance pathways. RAD18 governs at least two distinct mechanisms: translesion synthesis (TLS) and template switching (TS)-dependent pathways. Whereas TS is mainly error-free, TLS can work in an error-prone manner and, as such, the regulation of these pathways requires tight control to prevent DNA errors and potentially oncogenic transformation and tumorigenesis. In humans, the PCNA-associated recombination inhibitor (PARI) protein has recently been shown to inhibit homologous recombination (HR) events. Here, we describe a biochemical mechanism in which PARI functions as an HR regulator after replication fork stalling and during double-strand break repair. In our reconstituted biochemical system, we show that PARI inhibits DNA repair synthesis during recombination events in a PCNA interaction-dependent way but independently of its UvrD-like helicase domain. In accordance, we demonstrate that PARI inhibits HR in vivo, and its knockdown suppresses the UV sensitivity of RAD18-depleted cells. Our data reveal a novel human regulatory mechanism that limits the extent of HR and represents a new potential target for anticancer therapy. LA - English DB - MTMT ER - TY - JOUR AU - Baldeck, N AU - Janel-Bintz, R AU - Wagner, J AU - Tissier, A AU - Fuchs, RP AU - Burkovics, Péter AU - Haracska, Lajos AU - Despras, E AU - Bichara, M AU - Chatton, B AU - Cordonnier, AM TI - FF483-484 motif of human Poleta mediates its interaction with the POLD2 subunit of Poldelta and contributes to DNA damage tolerance. JF - NUCLEIC ACIDS RESEARCH J2 - NUCLEIC ACIDS RES VL - 43 PY - 2015 IS - 4 SP - 2116 EP - 2125 PG - 10 SN - 0305-1048 DO - 10.1093/nar/gkv076 UR - https://m2.mtmt.hu/api/publication/2858977 ID - 2858977 N1 - Biotechnologie et Signalisation Cellulaire, Universite de Strasbourg, Illkirch, 67412, France Inserm, Centre de Recherche en Cancerologie de Lyon, Lyon, 69000, France Cancer Research Center of Marseille, Centre National de la Recherche Scientifique, Unite Mixte de Recherche, Marseille, 13009, France Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged, HU-6726, Hungary Universite Paris-Sud, CNRS, Equipe Labellisee Ligue Contre le Cancer, Villejuif, France Cited By :17 Export Date: 11 May 2021 CODEN: NARHA Correspondence Address: Cordonnier, A.M.; Biotechnologie et Signalisation Cellulaire, Universite de StrasbourgFrance AB - Switching between replicative and translesion synthesis (TLS) DNA polymerases are crucial events for the completion of genomic DNA synthesis when the replication machinery encounters lesions in the DNA template. In eukaryotes, the translesional DNA polymerase eta (Poleta) plays a central role for accurate bypass of cyclobutane pyrimidine dimers, the predominant DNA lesions induced by ultraviolet irradiation. Poleta deficiency is responsible for a variant form of the Xeroderma pigmentosum (XPV) syndrome, characterized by a predisposition to skin cancer. Here, we show that the FF483-484 amino acids in the human Poleta (designated F1 motif) are necessary for the interaction of this TLS polymerase with POLD2, the B subunit of the replicative DNA polymerase delta, both in vitro and in vivo. Mutating this motif impairs Poleta function in the bypass of both an N-2-acetylaminofluorene adduct and a TT-CPD lesion in cellular extracts. By complementing XPV cells with different forms of Poleta, we show that the F1 motif contributes to the progression of DNA synthesis and to the cell survival after UV irradiation. We propose that the integrity of the F1 motif of Poleta, necessary for the Poleta/POLD2 interaction, is required for the establishment of an efficient TLS complex. LA - English DB - MTMT ER - TY - JOUR AU - Burkovics, Péter AU - Sebesta, M AU - Balogh, Dávid AU - Haracska, Lajos AU - Krejci, L TI - Strand invasion by HLTF as a mechanism for template switch in fork rescue. JF - NUCLEIC ACIDS RESEARCH J2 - NUCLEIC ACIDS RES VL - 42 PY - 2014 IS - 3 SP - 1711 EP - 1720 PG - 10 SN - 0305-1048 DO - 10.1093/nar/gkt1040 UR - https://m2.mtmt.hu/api/publication/2549960 ID - 2549960 N1 - PMC PMC3919600 AB - Stalling of replication forks at unrepaired DNA lesions can result in discontinuities opposite the damage in the newly synthesized DNA strand. Translesion synthesis or facilitating the copy from the newly synthesized strand of the sister duplex by template switching can overcome such discontinuities. During template switch, a new primer-template junction has to be formed and two mechanisms, including replication fork reversal and D-loop formation have been suggested. Genetic evidence indicates a major role for yeast Rad5 in template switch and that both Rad5 and its human orthologue, Helicase-like transcription factor (HLTF), a potential tumour suppressor can facilitate replication fork reversal. This study demonstrates the ability of HLTF and Rad5 to form a D-loop without requiring ATP binding and/or hydrolysis. We also show that this strand-pairing activity is independent of RAD51 in vitro and is not mechanistically related to that of another member of the SWI/SNF family, RAD54. In addition, the 3'-end of the invading strand in the D-loop can serve as a primer and is extended by DNA polymerase. Our data indicate that HLTF is involved in a RAD51-independent D-loop branch of template switch pathway that can promote repair of gaps formed during replication of damaged DNA. LA - English DB - MTMT ER - TY - JOUR AU - Burkovics, Péter AU - Sebesta, M AU - Sisakova, A AU - Plault, N AU - Szukacsov, Valéria AU - Robert, T AU - Pintér, Lajos AU - Marini, V AU - Kolesar, P AU - Haracska, Lajos AU - Gangloff, S AU - Krejci, L TI - Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis JF - EMBO JOURNAL J2 - EMBO J VL - 32 PY - 2013 IS - 5 SP - 742 EP - 755 PG - 14 SN - 0261-4189 DO - 10.1038/emboj.2013.9 UR - https://m2.mtmt.hu/api/publication/2422183 ID - 2422183 N1 - WoS:hiba:000316468000014 2019-03-03 20:42 első szerző nem egyezik AB - Completion of DNA replication needs to be ensured even when challenged with fork progression problems or DNA damage. PCNA and its modifications constitute a molecular switch to control distinct repair pathways. In yeast, SUMOylated PCNA (S-PCNA) recruits Srs2 to sites of replication where Srs2 can disrupt Rad51 filaments and prevent homologous recombination (HR). We report here an unexpected additional mechanism by which S-PCNA and Srs2 block the synthesis-dependent extension of a recombination intermediate, thus limiting its potentially hazardous resolution in association with a cross-over. This new Srs2 activity requires the SUMO interaction motif at its C-terminus, but neither its translocase activity nor its interaction with Rad51. Srs2 binding to S-PCNA dissociates Polδ and Polη from the repair synthesis machinery, thus revealing a novel regulatory mechanism controlling spontaneous genome rearrangements. Our results suggest that cycling cells use the Siz1-dependent SUMOylation of PCNA to limit the extension of repair synthesis during template switch or HR and attenuate reciprocal DNA strand exchanges to maintain genome stability. © 2013 European Molecular Biology Organization. LA - English DB - MTMT ER - TY - JOUR AU - Sebesta, M AU - Burkovics, Péter AU - Juhász, Szilvia AU - Zhang, SF AU - Szabó, Judit Eszter AU - Lee, MYWT AU - Haracska, Lajos AU - Krejci, L TI - Role of PCNA and TLS polymerases in D-loop extension during homologous recombination in humans JF - DNA REPAIR J2 - DNA REPAIR VL - 12 PY - 2013 IS - 9 SP - 691 EP - 698 PG - 8 SN - 1568-7864 DO - 10.1016/j.dnarep.2013.05.001 UR - https://m2.mtmt.hu/api/publication/2399209 ID - 2399209 AB - Homologous recombination (HR) is essential for maintaining genomic integrity, which is challenged by a wide variety of potentially lethal DNA lesions. Regardless of the damage type, recombination is known to proceed by RAD51-mediated D-loop formation, followed by DNA repair synthesis. Nevertheless, the participating polymerases and extension mechanism are not well characterized. Here, we present a reconstitution of this step using purified human proteins. In addition to Pol delta, TLS polymerases, including Pol eta and Pol kappa, also can extend D-loops. In vivo characterization reveals that Pol eta and Pol kappa are involved in redundant pathways for HR. In addition, the presence of PCNA on the D-loop regulates the length of the extension tracks by recruiting various polymerases and might present a regulatory point for the various recombination outcomes. (c) 2013 The Authors. Published by Elsevier B.V. All rights reserved. LA - English DB - MTMT ER -