Naslov
Cisplatin-induced apoptotic death of CL-V5B cells hypersensitive to cross-linking agents is due to erroneous checkpoint control rather than impaired DNA damage removal

Autori
Brozović, Anamaria ; Damrot, Julia ; Tsaryk, Roman ; Nikolova, Theodora ; Hartig, Cornelia ; Zdzienicka, Malgorzata Z ; Osmak, Maja ; Ross, Wynand ; Kaina, Bernd ; Fritz, Gerhard

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
EEMS 38th Annual Meeting Program and Abstract / - , 2008

Skup
EEMS 38th Annual Meeting

Mjesto i datum
Cavtat, Hrvatska, 21.09.2008. - 25.09.2008

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
cisplatina; stanična smrt; kontrola staničnog ciklusa
(cisplatin; cell death; checkpoint control)

Sažetak
A pair of isogenic Chinese hamster cell lines differing in their Fanconi anemia status was used to investigate cisplatin (cDDP)-induced cell death. FANCC defective cells (CL-V5B) are hypersensitive to cDDP, compared to wild type (V79) cells, even though they showed a cca. 50% less initial DNA adduct formation than the wild type. Moreover, cDDP-triggered early stress responses, phosphorylation of histone H2AX and c-jun N-terminal kinase (JNK), are attenuated in CL-V5B cells. However, CL-V5B cells display an excessive G2/M arrest, extensive formation of chromosomal aberrations (CA) and increased formation of gamma-H2AX foci 24 h after cDDP treatment. CL-V5B cells are proficient in DNA adducts removal and show functional homologous recombination, since the frequency of sister chromatid exchanges was similar to this of the wild type. Inhibition of ataxia-telangiectasia mutated kinase /ATM)/ATM and Rad3-related kinase (ATR) signalling by caffeine abrogates G2/M arrest in both cell lines, but only wild type cells were sensitised to cDDP. Thus, our data suggest that S phase-dependent processing of cDDP-induced interstrand cross-links is erroneous in FANCC defective CL-V5B cells, resulting in excessive formation of secondary DNA lesions, which in turn give rise to trapping of cells in G2/M, massive formation of CA and apptotic cell death.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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