"2009-01-01+01:00"^^ . "1"^^ . "679"^^ . "1"^^ . "2010-12-31+01:00"^^ . "679"^^ . "Targeting DNA repair genes in engineered human cancer cells deficient in BRCA2, FANCC and FANCG"@en . "Geny sign\u00E1ln\u00ED dr\u00E1hy Fanconiho an\u00E9mie (FA) BRCA2, FANCC, FANCG jsou inaktivov\u00E1ny u \u0159ady sporadick\u00FDch n\u00E1dor\u016F. Jejich absence biochemicky odli\u0161uje mutovan\u00E9 bu\u0148ky, p\u0159edev\u0161\u00EDm jejich neschopnost\u00ED opravovat mezi\u0159et\u011Bzcov\u00E9 m\u016Fstky homologn\u00ED rekombinac\u00ED (HR). Ned\u00E1vno byla implikov\u00E1na \u00FA\u010Dast gen\u016F opravuj\u00EDc\u00EDch DNA pomoc\u00ED excise nukleotid\u016F (NER) v odstra\u0148ov\u00E1n\u00ED mytomycinem zp\u016Fsoben\u00FDch mezi\u0159et\u011Bzcov\u00FDch m\u016Fstk\u016F. Dokonce p\u0159i chyb\u011Bn\u00ED n\u011Bkter\u00FDch NER gen\u016F m\u016F\u017Ee z\u00E1stava replikace zp\u016Fsoben\u00E1 po\u0161kozen\u00EDm DNA dokonce indukovat vznik zlomenin obou \u0159et\u011Bzc\u016F DNA (DSB). Bu\u0148ky deficitn\u00ED v HR tedy mohou b\u00FDt selektivn\u011B citliv\u00E9 k exogenn\u00ED inhibici t\u011Bchto gen\u016F. S c\u00EDlem bl\u00ED\u017Ee pochopit machanismy opravy DNA a p\u0159\u00EDpadn\u011B objevit nov\u00E9 terapeutick\u00E9 c\u00EDle v na\u0161ich BRCA2, FANCC a FANCG deficitn\u00EDch bu\u0148k\u00E1ch, budeme sledovat d\u016Fsledky inhibice NER gen\u016F na vznik DSB a p\u0159e\u017Eit\u00ED v na\u0161ich dob\u0159e kontrolovan\u00FDch lidsk\u00FDch n\u00E1dorov\u00FDch knock-out modelech."@cs . . "0"^^ . . . . . "Fanconi anemia; BRCA2; FANCC; FANCG; homologou recombination; mitomycin C, nucleotide excision repair; translesional polymerase; siRNA"@en . . . . . "1"^^ . "Inhibice gen\u016F \u00FA\u010Dastn\u00EDc\u00EDch se opravy DNA u BRCA2, FANCC a FANCG deficitn\u00EDch bun\u011Bk"@cs . "0"^^ . "Fanconi anemia (FA) genes BRCA2, FANCC and FANCG are inactivated in a variety of sporadic tumors. Their absence causes an absolute biochemical difference in mutated cells, mainly impaired ability to repair interstrand crosslinks by homologous recombination (HR). Nucleotide excision repair (NER) genes including translesional polymerases have recently been implicated in removal of mitomycin-induced interstrand cross-links. Furthermore, in absence of these genes, stalled replication forks induced by DNA damage may result in induction of double strand breaks (DSB). HR-deficient cells may thus be selectively sensitive to exogenous inhibition of these genes. In order to gain further insight into the mechanisms of DNA repair machinary and possibly discover new therapeutic targets in our BRCA2, FANCC and FANCG deficient cells , we will explore the effects of inhibition of genes involved in NER on DSB induction and survival in our well-controlled engineered human cancer FA knock-out cells."@en . .