γH2AX prefers late replicating metaphase chromosome regions

Publication date: Available online 4 June 2018Source: Mutation Research/Genetic Toxicology and Environmental MutagenesisAuthor(s): Ana Laura Reyes-Ábalos, Pablo Liddle, Gustavo A. Folle, María Vittoria Di TomasoAbstractDNA damage response (DDR) constitutes a protein pathway to handle eukaryotic DNA lesions in the context of chromatin. DDR engages the recruitment of signaling, transducer, effector, chromatin modifiers and remodeling proteins, allowing cell cycle delay, DNA repair or induction of senescence or apoptosis. An early DDR-event includes the epigenetic phosphorylation of the histone variant H2AX on serine 139 of the C-termini, so-called gammaH2AX. GammaH2AX foci detected by immunolabeling on interphase nuclei have been largely studied; nonetheless gammaH2AX signals on mitotic chromosomes are less understood. The CHO9 cell line is a subclone of CHO (Chinese hamster ovary) cells with original and rearranged Z chromosomes originated during cell line transformation. As a result, homologous chromosome regions have been relocated in different Z-chromosomes. In a first quantitative analysis of gammaH2AX signals on immunolabeled mitotic chromosomes of cytocentrifuged metaphase spreads, we reported that gammaH2AX139 signals of both control and bleomycin-exposed cultures showed statistically equal distribution between CHO9 homologous chromosome regions, suggesting a possible dependence on the structure/function of chromatin. We have also demonstrated that bleomycin-induced g...

Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - July 6, 2018 Category: Genetics & Stem Cells Source Type: research