Ionizing Radiation Triggers Chromatin-bound kin17 Complex Formation in Human Cells

Denis S. F. Biard, Laurent Miccoli, Emmanuelle Despras, Yveline Frobert, Christophe Créminon, Jaime F. Angulo
2002 Journal of Biological Chemistry  
The human DNA-binding HSA kin17 protein cross-reacts with antibodies raised against the stress-activated Escherichia coli RecA protein. We show here that HSA kin17 protein is directly associated with chromosomal DNA as judged by cross-linking experiments on living cells. We detected increased amounts of DNAbound HSA kin17 protein 24 h after ␥ irradiation, with 2.6-fold more HSA kin17 molecules after 6 Gy of irradiation (46,000 -117,000 molecules). At this time we observed that highly
more » ... ng RKO cells displayed the concentration and co-localization of HSA kin17 and replication protein A in nucleoplasmic foci. Our results suggest that 24 h post-irradiation HSA kin17 protein may localize at the sites of unrepaired DNA damages. RKO clones expressing an HSA KIN17 antisense transcript (RASK.5 and RASK.13 cells) revealed that reduced HSA kin17 protein levels are correlated with a decrease in clonogenic cell growth and cell proliferation, as well as an accumulation of cells in early and mid-S phase. Taken together our observations support the idea that HSA kin17 protein is a DNA maintenance protein involved in the cellular response to the presence of DNA damage and suggest that it helps to overcome the perturbation of DNA replication produced by unrepaired lesions.
doi:10.1074/jbc.m200321200 pmid:11880372 fatcat:oumcajov2feublccmycjqwakny