. . . "2013-10-31+01:00"^^ . " chromosome aberations" . . "human embryonic stem cells; chromosome aberations; base excision repair; apurinic/apyrimidinic endonucl"@en . . "Mechanism responsible for BER failure during long term cultivation of hESC was identified including induction of responsible enzyme APE1 by statins. Model with downregulated expression of APE1 and method to detect genome stability were developed."@en . "2011-08-08+02:00"^^ . . . "0"^^ . " base excision repair" . . . . . "Identifikace mechanizm\u016F vzniku chromozom\u00E1ln\u00EDch aberac\u00ED p\u0159i dlouhodob\u00E9 kultivaci lidsk\u00FDch embryon\u00E1ln\u00EDch bun\u011Bk in vitro" . "Projekt p\u0159edpokl\u00E1d\u00E1 kultivaci nejm\u00E9n\u011B dvou nez\u00E1visl\u00FDch lini\u00ED hESC ve form\u011B \u010Dasn\u00E9 (do pas\u00E1\u017Ee cca 40), st\u0159edn\u00ED a pozdn\u00ED pas\u00E1\u017Ee (200-300 pas\u00E1\u017E\u00ED). U t\u011Bchto bun\u011Bk budou stanoveny aktivity hlavn\u00EDch proces\u016F ovliv\u0148uj\u00EDc\u00EDch v\u00FDskyt chromozom\u00E1ln\u00EDch aberac\u00ED, jako je udr\u017Eba telomer a opravn\u00E9 machanizmy DNA, \u010D\u00EDtaj\u00EDc\u00ED opravu dvou\u0159et\u011Bzvov\u00FDch zlom\u016F (p\u0159edev\u0161\u00EDm NHEJ) a po\u0161kozen\u00FDch b\u00E1z\u00ED (p\u0159edev\u0161\u00EDm BER). Skute\u010Dn\u00FD vliv poklesu APE/Ref1 bude ov\u011B\u0159en pou\u017Eit\u00EDm siRNA. Bude otestov\u00E1n vliv statin\u016F na aktivitu APE/Ref1, pota\u017Emo pak BER, coby l\u00E1tek, kter\u00E9 maj\u00ED aktiva\u010Dn\u00ED vliv na biochemick\u00E9 cesty zapojen\u00E9 v angiogenezi a \u010D\u00EDtaj\u00EDc\u00ED APE/Ref1 endonukle\u00E1zu. C\u00EDlem projektu je identifikovat procesy, kter\u00E9 zp\u016Fsobuj\u00ED zv\u00FD\u0161en\u00FD v\u00FDskyt chromozom\u00E1ln\u00EDch aberac\u00ED u hESC dlouhodob\u011B kultivovan\u00FDch in vitro, p\u0159\u00EDpadn\u011B identifikovat l\u00E1tky, kter\u00E9 by tento proces mohly zpomali, \u010Di zastavit." . "1"^^ . . "0"^^ . "1"^^ . "human embryonic stem cells" . "http://www.isvav.cz/projectDetail.do?rowId=NS10237"^^ . "1"^^ . . "Byl identifikov\u00E1n enzym zodpov\u011Bdn\u00FD za pokles BER p\u0159i dlouhodob\u00E9 kultivaci lidsk\u00FDch ESC, apurinn\u00ED/apyrimidinn\u00ED endonukl\u00E1za APE1, a indukce tohoto enzymu statiny. Byl vytvo\u0159en model se sn\u00ED\u017Eenou expres\u00ED APE1 a metoda detekce stability genomu."@cs . . "NS10237" . "Disection of mechanism behind chromosomal aberation cumulation during long term cultivation of human embryonic stem cells."@en . "2011-12-31+01:00"^^ . . . "2009-01-01+01:00"^^ . . . "At least two independent lines of hESC will be tested as early (<40 passages), medium and late (200-300 passages) passage. Activities of major processes, such as telomer maintennance, DNA repair including non homologous end joining (NHEJ) and BER, involved in genome integrity maintenance will be assayed and related to passage. Real influence of APE/Ref1 expression downregulation will be verified using siRNA. Statins are compounds with positive effect on angiogenesis via pathways including APE/Ref1. Effect of statins on APE/Ref1 in hES will be assessed. The major aim of the project is to identify the processes, which promote accumulation of chromosomal aberations long term cultured hESC and identify compound with potential to slow or stop this process."@en . . .