TY - JOUR AU - Mórocz, Mónika AU - Qorri, Erda AU - Pekker, Emese AU - Tick, Gabriella AU - Haracska, Lajos TI - Exploring RAD18-dependent replication of damaged DNA and discontinuities: A collection of advanced tools JF - JOURNAL OF BIOTECHNOLOGY J2 - J BIOTECHNOL VL - 380 PY - 2024 SP - 1 EP - 19 PG - 19 SN - 0168-1656 DO - 10.1016/j.jbiotec.2023.12.001 UR - https://m2.mtmt.hu/api/publication/34489854 ID - 34489854 N1 - Funding Agency and Grant Number: European Union [739593, RRF-2.3.1-21-2022-00015]; National Research, Development, and Innovation Office [TKP-31-8/PALY-2021, 2020-1.1.2-PIACI-KFI-2021-00304]; (European Union) Funding text: This project received Funding from the European Union ' s Horizon 2020 research and innovation program under grant agreement No. 739593. This work was also supported by the National Research, Development, and Innovation Office (TKP-31-8/PALY-2021 and 2020-1.1.2-PIACI-KFI-2021-00304) . Project no. RRF-2.3.1-21-2022-00015 has been implemented with the support provided by the European Union) . AB - DNA damage tolerance (DDT) pathways mitigate the effects of DNA damage during replication by rescuing the replication fork stalled at a DNA lesion or other barriers and also repair discontinuities left in the newly replicated DNA. From yeast to mammalian cells, RAD18-regulated translesion synthesis (TLS) and template switching (TS) represent the dominant pathways of DDT. Monoubiquitylation of the polymerase sliding clamp PCNA by HRAD6A-B/RAD18, an E2/E3 protein pair, enables the recruitment of specialized TLS polymerases that can insert nucleotides opposite damaged template bases. Alternatively, the subsequent polyubiquitylation of monoubiquitin-PCNA by Ubc13-Mms2 (E2) and HLTF or SHPRH (E3) can lead to the switching of the synthesis from the damaged template to the undamaged newly synthesized sister strand to facilitate synthesis past the lesion. When immediate TLS or TS cannot occur, gaps may remain in the newly synthesized strand, partly due to the repriming activity of the PRIMPOL primase, which can be filled during the later phases of the cell cycle. The first part of this review will summarize the current knowledge about RAD18-dependent DDT pathways, while the second part will offer a molecular toolkit for the identification and characterization of the cellular functions of a DDT protein. In particular, we will focus on advanced techniques that can reveal single-stranded and doublestranded DNA gaps and their repair at the single-cell level as well as monitor the progression of single replication forks, such as the specific versions of the DNA fiber and comet assays. This collection of methods may serve as a powerful molecular toolkit to monitor the metabolism of gaps, detect the contribution of relevant pathways and molecular players, as well as characterize the effectiveness of potential inhibitors. LA - English DB - MTMT ER - TY - JOUR AU - Li, Qiuzhen AU - Dudás, Kata AU - Tick, Gabriella AU - Haracska, Lajos TI - Coordinated Cut and Bypass: Replication of Interstrand Crosslink-Containing DNA JF - FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY J2 - FRONT CELL DEV BIOL VL - 9 PY - 2021 PG - 8 SN - 2296-634X DO - 10.3389/fcell.2021.699966 UR - https://m2.mtmt.hu/api/publication/32106322 ID - 32106322 N1 - Funding Agency and Grant Number: European Union's Horizon 2020 Research and Innovation Programme [739593]; National Research, Development and Innovation OfficeNational Research, Development & Innovation Office (NRDIO) - Hungary [GINOP-2.3.2-15-2016-00024, GINOP-2.3.2-15-2016-00026] Funding text: This project received funding from the European Union's Horizon 2020 Research and Innovation Programme under Grant Agreement No. 739593. This work was also supported by the National Research, Development and Innovation Office GINOP2.3.2-15-2016-00024 and GINOP-2.3.2-15-2016-00026. HCEMM-BRC Mutagenesis and Carcinogenesis Research Group, Institute of Genetics, Biological Research Centre, Szeged, Hungary Mutagenesis and Carcinogenesis Research Group, Institute of Genetics, Biological Research Centre, Szeged, Hungary Export Date: 31 August 2021 Correspondence Address: Haracska, L.; HCEMM-BRC Mutagenesis and Carcinogenesis Research Group, Hungary; email: haracska.lajos@brc.hu HCEMM-BRC Mutagenesis and Carcinogenesis Research Group, Institute of Genetics, Biological Research Centre, Szeged, Hungary Mutagenesis and Carcinogenesis Research Group, Institute of Genetics, Biological Research Centre, Szeged, Hungary Export Date: 16 September 2021 Correspondence Address: Haracska, L.; HCEMM-BRC Mutagenesis and Carcinogenesis Research Group, Hungary; email: haracska.lajos@brc.hu HCEMM-BRC Mutagenesis and Carcinogenesis Research Group, Institute of Genetics, Biological Research Centre, Szeged, Hungary Mutagenesis and Carcinogenesis Research Group, Institute of Genetics, Biological Research Centre, Szeged, Hungary Export Date: 17 September 2021 Correspondence Address: Haracska, L.; HCEMM-BRC Mutagenesis and Carcinogenesis Research Group, Hungary; email: haracska.lajos@brc.hu AB - DNA interstrand crosslinks (ICLs) are covalently bound DNA lesions, which are commonly induced by chemotherapeutic drugs, such as cisplatin and mitomycin C or endogenous byproducts of metabolic processes. This type of DNA lesion can block ongoing RNA transcription and DNA replication and thus cause genome instability and cancer. Several cellular defense mechanism, such as the Fanconi anemia pathway have developed to ensure accurate repair and DNA replication when ICLs are present. Various structure-specific nucleases and translesion synthesis (TLS) polymerases have come into focus in relation to ICL bypass. Current models propose that a structure-specific nuclease incision is needed to unhook the ICL from the replication fork, followed by the activity of a low-fidelity TLS polymerase enabling replication through the unhooked ICL adduct. This review focuses on how, in parallel with the Fanconi anemia pathway, PCNA interactions and ICL-induced PCNA ubiquitylation regulate the recruitment, substrate specificity, activity, and coordinated action of certain nucleases and TLS polymerases in the execution of stalled replication fork rescue via ICL bypass. LA - English DB - MTMT ER - TY - JOUR AU - Török, István AU - Herrmann-Horle, D AU - Kiss, István AU - Tick, Gabriella AU - Speer, Gábor AU - Schmitt, R AU - Mechler, BM TI - Down-regulation of RpS21, a putative translation initiation factor interacting with P40, produces viable minute imagos and larval lethality with overgrown hematopoietic organs and imaginal discs. JF - MOLECULAR AND CELLULAR BIOLOGY J2 - MOL CELL BIOL VL - 19 PY - 1999 IS - 3 SP - 2308 EP - 2321 PG - 14 SN - 0270-7306 UR - https://m2.mtmt.hu/api/publication/1335576 ID - 1335576 N1 - SI: GENBANK/AJ009557 PMC: PMC84023 OID: NLM: PMC84023 AB - Down-regulation of the Drosophila ribosomal protein S21 gene (rpS21) causes a dominant weak Minute phenotype and recessively produces massive hyperplasia of the hematopoietic organs and moderate overgrowth of the imaginal discs during larval development. Here, we show that the S21 protein (RpS21) is bound to native 40S ribosomal subunits in a salt-labile association and is absent from polysomes, indicating that it acts as a translation initiation factor rather than as a core ribosomal protein. RpS21 can interact strongly with P40, a ribosomal peripheral protein encoded by the stubarista (sta) gene. Genetic studies reveal that P40 underexpression drastically enhances imaginal disc overgrowth in rpS21-deficient larvae, whereas viable combinations between rpS21 and sta affect the morphology of bristles, antennae, and aristae. These data demonstrate a strong interaction between components of the translation machinery and showed that their underexpression impairs the control of cell proliferation in both hematopoietic organs and imaginal discs. LA - English DB - MTMT ER - TY - JOUR AU - Tick, Gabriella AU - Cserpán, Imre AU - Dombrádi, Viktor Béla AU - Mechler, BM AU - Török, István AU - Kiss, István TI - Structural and functional characterization of the Drosophila glycogen phosphorylase gene JF - BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS J2 - BIOCHEM BIOPH RES CO VL - 257 PY - 1999 IS - 1 SP - 34 EP - 43 PG - 10 SN - 0006-291X DO - 10.1006/bbrc.1999.0396 UR - https://m2.mtmt.hu/api/publication/1122212 ID - 1122212 LA - English DB - MTMT ER - TY - JOUR AU - OHKURA, H AU - Török, Tibor AU - Tick, Gabriella AU - HOHEISEL, J AU - Kiss, István AU - GLOVER, MD TI - Mutation of a gene for a Drosophila kinesin-like protein, Klp38B , leads to failure of cytokinesis. JF - JOURNAL OF CELL SCIENCE J2 - J CELL SCI VL - 110 PY - 1997 SP - 945 EP - 954 PG - 10 SN - 0021-9533 UR - https://m2.mtmt.hu/api/publication/1906653 ID - 1906653 LA - English DB - MTMT ER - TY - JOUR AU - Török, István AU - STRAND, D AU - SCHMIDT, R AU - Tick, Gabriella AU - Török, Tibor AU - Kiss, István AU - MECHLER, BM TI - The overgrown hematopoietic organs-31 tumor suppressor gene of Drosophila encodes an importin-like protein accumulating in the nucleus at the onset of mitosis. JF - JOURNAL OF CELL BIOLOGY J2 - J CELL BIOL VL - 129 PY - 1995 SP - 1473 EP - 1489 PG - 17 SN - 0021-9525 DO - 10.1083/jcb.129.6.1473 UR - https://m2.mtmt.hu/api/publication/1906080 ID - 1906080 LA - English DB - MTMT ER - TY - JOUR AU - Török, Tibor AU - Tick, Gabriella AU - Alvarado, Márta AU - Kiss, István TI - P-lacW insertional mutagenesis on the second chromosome of Drosophila melanogaster: isolation of lethals with different overgrowth phenotypes. JF - GENETICS J2 - GENETICS VL - 135 PY - 1993 SP - 71 EP - 80 PG - 10 SN - 0016-6731 UR - https://m2.mtmt.hu/api/publication/1905471 ID - 1905471 LA - English DB - MTMT ER -