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Roles of nibrin and ATM/ATR kinases on the G2 checkpoint under endogenous or radio-induced DNA damage Biol. Res.
Marcelain,Katherine; de la Torre,Consuelo; González,Patricio; Pincheira,Juana.
Checkpoint response to DNA damage involves the activation of DNA repair and G2 lengthening subpathways. The roles of nibrin (NBS1) and the ATM/ATR kinases in the G2 DNA damage checkpoint, evoked by endogenous and radio-induced DNA damage, were analyzed in control, A-T and NBS lymphoblast cell lines. Short-term responses to G2 treatments were evaluated by recording changes in the yield of chromosomal aberrations in the ensuing mitosis, due to G2 checkpoint adaptation, and also in the duration of G2 itself. The role of ATM/ATR in the G2 checkpoint pathway repairing chromosomal aberrations was unveiled by caffeine inhibition of both kinases in G2. In the control cell lines, nibrin and ATM cooperated to provide optimum G2 repair for endogenous DNA damage. In...
Tipo: Journal article Palavras-chave: Ataxia-telangiectasia; ATM; ATR kinases; Caffeine; G2 checkpoint; Nibrin (Nbs1); Nijmegen breakage syndrome (NBS).
Ano: 2005 URL: http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602005000200007
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Response of the G2-prophase checkpoint to genotoxic drugs in lymphocytes from healthy individuals Biol. Res.
Pincheira,Juana; de la Torre,Consuelo; Rodríguez,Natalie; Valenzuela,Carlos Y.
We analyzed the in vitro effects of the anti-tumoral drugs doxorubicin, cytosine arabinoside and hydroxyurea on the G2-prophase checkpoint in lymphocytes from healthy individuals. At biologically equivalent concentrations, the induced DNA damage activated the corresponding checkpoint. Thus: i) there was a concentration-dependent delay of G2 time and an increase of both the total DNA lesions produced and repaired before metaphase and; ii) G2-checkpoint adaptation took place as chromosome aberrations (CAs) started to appear in the metaphase, indicating the presence of unrepaired double-strand breaks (DSBs) in the previous G2. The checkpoint ATM/ATR kinases are involved in DSB repair, since the recorded frequency of CAs increased when both kinases were...
Tipo: Journal article Palavras-chave: DNA damage and repair; G2-prophase checkpoint adaptation; Premitotic DSBs and chromosomal aberrations; Anti-tumoral genotoxic drugs.
Ano: 2012 URL: http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602012000200010
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