1. ¹Apoptosis Research Group, Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada K1A 0R6
2. ²Department of Cell and Molecular Biology, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA

Correspondence: M Sikorska and QY Liu, Apoptosis Research Group, Institute for Biological Sciences, National Research Council of Canada, 1200 Montreal Road, Bldg M-54, Ottawa, Ontario, Canada K1A 0R6. Tel: +1 613 993 5916 or +1 613 990 0850; Fax: +1 613 990 7963; E-mail: marianna.sikorska@nrc.ca

Received 8 July 2002; Revised 4 September 2002; Accepted 16 September 2002.

Abstract

Apoptotic DNA degradation could be initiated by the accumulation of single-strand (ss) breaks in vulnerable chromatin regions, such as base unpairing regions (BURs), which might be preferentially targeted for degradation by both proteases and nucleases. We tested this hypothesis in anti-Fas-treated apoptotic Jurkat cells. Several nuclear proteins known for their association with both MARs and the nuclear matrix, that is, PARP, NuMA, lamin B and SATB1, were degraded, but the morphological rearrangement of the BUR-binding SATB1 protein was one of the earliest detected changes. Subsequently, we have identified several genes containing sequences homologous to the 25 bp BUR element of the IgH gene, a known SATB1-binding site, and examined the integrity of genomic DNA in their vicinity. Multiple ss breaks were found in close proximity to these sites relative to adjacent regions of DNA. Consistent with our prediction, the results indicated that the initiation of DNA cleavage in anti-Fas-treated Jurkat cells occurred within the BUR sites, which likely became accessible to endonucleases due to the degradation of BUR-binding proteins.