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001-es BibID:	BIBFORM079818
035-os BibID:	(cikkazonosító)102642 (Scopus)85068486502 (PMID)31300387
Első szerző:	Boros-Oláh Beáta (molekuláris biológus)
Cím:	Drugging the R-loop interactome : RNA-DNA hybrid binding proteins as targets for cancer therapy / Beáta Boros-Oláh, Nikoletta Dobos, Lilla Hornyák, Zoltán Szabó, Zsolt Karányi, Gábor Halmos, Jason Roszik, Lóránt Székvölgyi
Dátum:	2019
ISSN:	1568-7864
Megjegyzések:	Unravelling the origin of genetic alterations from point mutations to chromosomal rearrangements was greatly enhanced by the discovery of RNA-DNA hybrids (R-loops) that behave as hotspots of genomic instability in a variety of organisms. Current models suggest that uncontrolled R-loops are a hazard to genome integrity, therefore, identifying proteins that are involved in recognising and signalling R-loop structures are of key importance. Herein we analysed key RNA-DNA hybrid binding proteins in humans taking advantage of large-scale gene expression, survival rate, and drug-sensitivity data from cancer genomics databases. We show that ex- pression of RNA-DNA hybrid binding proteins in various cancer types is associated with survival and may have contrasting outcomes in responding to therapeutic treatments. Based on the revealed pharmacogenomic land- scape of human RNA-DNA hybrid binding proteins, we propose that R-loops and R-loop binding proteins are potentially relevant new epigenetic markers and therapeutic targets in multiple cancers
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Cancer diagnostics and therapy Chemotherapy Clinical trial Drug sensitivity R-loop RNA-DNA hybrid Survival association
Megjelenés:	DNA Repair. - 84 (2019), p. 1-10. -
További szerzők:	Dobos Nikoletta (1981-) (biológus) Hornyák Lilla Szabó Zoltán (1973-) (belgyógyász, kardiológus) Karányi Zsolt (1961-) (biostatisztikus, bioinformatikus) Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Roszik, Jason Székvölgyi Lóránt (1977-) (biofizikus, biokémikus, sejtbiológus)
Pályázati támogatás:	GINOP-2.3.2-15-2016-00024 GINOP GINOP-2.3.2-15-2016-00043 GINOP GINOP-2.3.2-15-2016-00062 GINOP Lendület program LP2015-9/2015 egyéb 20428-3/2018/FEKUTSTRAT egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM016570
Első szerző:	Varga Tamás (biológus)
Cím:	Chromosomal aberrations induced by double strand DNA breaks / Varga Tamas, Aplan Peter D.
Dátum:	2005
ISSN:	1568-7864
Megjegyzések:	It has been suggested that introduction of double-strand DNA breaks into mammalian chromosomes can lead to gross chromosomal rearrangements through improper DNA repair. To study this phenomenon, we employed a model system in which a double-strand DNA break (DSB) can be produced in human cells in vivo at a predetermined location. The ensuing chromosomal changes flanking the breakage site can then be cloned and characterized. In this system, the recognition site for the I-SceI endonuclease, whose 18 bp recognition sequence is not normally found in the human genome, is placed between a strong constitutive promoter and the Herpes simplex virus thymidine kinase (HSV-tk) gene, which serves as a negative selectable marker. We found that the most common mutation following aberrant DSB repair was an interstitial deletion; these deletions typically showed features of non-homologous end joining (NHEJ), such as microhomologies and insertions of direct or inverted repeat sequences. We also detected more complex rearrangements, including large insertions from adjacent or distant genomic regions. The insertion events that involved distant genomic regions typically represented transcribed sequences, and included both L1 LINE elements and sequences known to be involved in genomic rearrangements. This type of aberrant repair could potentially lead to gene inactivation via deletion of coding or regulatory sequences, or production of oncogenic fusion genes via insertion of coding sequences.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Chromosomal rearrangement Double strand DNA break I-SceI Insertion Non-homologous end joining
Megjelenés:	Dna Repair. - 4 : 9 (2005), p. 1038-1046. -
További szerzők:	Aplan, Peter D.
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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