Onset of Chromatin Fragmentation in Chloroma Cell Apoptosis Is Highly Sensitive to UV and Begins at Non-B DNA Conformation

Abstract

UV irradiation induces programmed death, or apoptosis, in rat chloroleukaemia cells, a process characterized by typical cell morphology, fragmentation of chromatin into units of single and multiple nucleosomes, and transcriptional activation of LINE. Our study shows that this process is initiated by very low UV doses: exposure to one minimal erythema dose (MED, about 200 J/m²), at defined wavelengths ranging from 270 to 330 nm, is sufficient. By sequencing 100 randomly selected blunt-end chromatin fragments (single and multiple nucleosomes) we observed that at an early stage of apoptosis the fragmented DNA contains a four-fold excess of both long and short interspersed nuclear retroelements (LINEs and SINEs). A distinct sequence finding was also the observation that fragmented DNA is very rich in microsatellites, (CA)_n dinucleotides in particular, and in long stretches of homopurine/homopyrimidine domains. The present results thus indicate that chromatin fragmentation in UV-induced apoptosis begins at non-random locations involving non-B DNA conformation, and that the onset of the suicide process in chloroleukaemia cells is surprisingly sensitive to UV exposure.