Pol kappa partially rescues MMR-dependent cytotoxicity of O6-methylguanine
作者： Eliana Lupari , Ilenia Ventura , Francesca Marcon , Gabriele Aquilina , Eugenia Dogliotti
DOI: 10.1016/J.DNAREP.2012.03.004
关键词:
摘要: To maintain genomic integrity cells have to respond properly a variety of exogenous and endogenous sources DNA damage. is maintained by the coordinated action damage response mechanisms repair. In addition, there are also tolerance, such as translesion synthesis (TLS), which important for survival after but potentially error-prone. Here, we investigate role polymerase κ (pol κ) in TLS across alkylated lesions silencing this (pol) human using transient small RNA interference. We show that pol has significant protective against methyl nitrosourea (MNU)-associated cytotoxicity without affecting significantly mutagenicity. The increase MNU-induced when down-regulated was affected levels O6-methylguanine methyltransferase fully abolished mismatch repair (MMR) defective. Following MNU treatment, cell cycle profile unaffected status. downregulation caused severe delay onset second mitosis dependent on presence ( O6-meGua) lesions. After exposure, absence κ, frequency sister chromatid exchanges whereas induction RAD 51 foci increased. propose partially protects from MMR-dependent O6-meGua restoring replicated duplexes containing single-stranded gaps generated opposite facilitated binding.
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