H2ac depletion induces chromosomal abnormalities.

Telomeric FISH on metaphases spreads from MCF-7 cells with siH2ac. The telomeric hybridization signal is shown in red and DAPI-counterstained chromosomes in blue. (A) Representative images of normal telomeric DNA signals (in red) and chromosomes (in blue). (B-F) Representative images of multiple chromosome abnormalities. Knockdown of H2ac induced multiple chromosomal aberrations, including chromosome with telomere free ends (B); sister-chromatid telomere losses (C); chromosome fusions with or without TTAGGG repeats at the fusion sites (D); chromatid fusions (E); and chromosome breakages (F). The frequency of cytogenetic aberrations is quantitated under each panel. (G) The induction of anaphase bridges and micronuclei is shown. MCF-7 and IMR-90 cells were harvested at day 6 after two separate transfections with control or H2ac siRNAs. The black-and-white images showed DNA staining by DAPI. Quantification of DAPI-positive anaphase bridges and micronuclei in control or H2ac siRNA-treated in MCF-7 or IMR-90 cells. (n = 100, the P value was calculated using a Student's two-tailed t-test.).