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The novel SAR‐binding domain of scaffold attachment factor A (SAF‐A) is a target in apoptotic nuclear breakdown
Author(s) -
Göhring Frank,
Schwab Birgit L.,
Nicotera Pierluigi,
Leist Marcel,
Fackelmayer Frank O.
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.24.7361
Subject(s) - biology , microbiology and biotechnology , scaffold , apoptosis , scaffold protein , dna binding protein , biophysics , signal transduction , transcription factor , biochemistry , biomedical engineering , engineering , gene
The scaffold attachment factor A (SAF‐A) is an abundant component of the nuclear scaffold and of chromatin, and also occurs in heterogeneous nuclear ribonucleoprotein (hnRNP) complexes. Evidence from previous experiments had suggested that SAF‐A most likely has at least two different functions, being involved both in nuclear architecture and RNA metabolism. We now show that the protein has a novel scaffold‐associated region (SAR)‐specific bipartite DNA‐binding domain which is independent from the previously identified RNA‐binding domain, the RGG box. During apoptosis, but not during necrosis, SAF‐A is cleaved in a caspase‐dependent way. Cleavage occurs within the bipartite DNA‐binding domain, resulting in a loss of DNA‐binding activity and a concomitant detachment of SAF–A from nuclear structural sites. On the other hand, cleavage does not compromise the association of SAF‐A with hnRNP complexes, indicating that the function of SAF‐A in RNA metabolism is not affected in apoptosis. Our results suggest that detachment of SAF–A from SARs, caused by apoptotic proteolysis of its DNA‐binding domain, is linked to the formation of oligonucleosomal‐sized DNA fragments and could therefore contribute to nuclear breakdown in apoptotic cells.