LINE L1 retrotransposable element is targeted during the initial stages ofapoptotic DNA fragmentation

Using a directional cloning strategy, DNA sequence information was obtained corresponding to the site of early radiation-induced apoptotic DNA fragmen tation within the human lymphoblastoid cell line TK6. Data were obtained fr om 88 distinct clones comprising approximately 65 kbp of sequenced material . Analysis of all cloned material showed that sequences in the 10 bp immedi ately adjacent to the cleavage sites were enriched in short oligoT tracts. The proportion of repetitive DNA within the entire cloned material was foun d to be within the normal range. However the distribution of Alu and LINE r epetitive DNA were biased to positions at or adjacent to the apoptotic clea vage site. In particular, a non-random distribution of five cleavage sites was found clustered within the second ORF of the LINE L1 that partially ove rlapped with two binding sites for the nuclear matrix-associated protein SA TB1. Three other clones, containing alpha satellite elements, were also lin ked to a DNA matrix binding function. These data indicate that the site of chromatin loop formation at the nuclear matrix may be a specific target for early DNA fragmentation events during apoptosis. (C) 2000 Wiley-Liss, Inc.