The novel SAR-binding domain of scaffold attachment factor A (SAF-A) is a target in apoptotic nuclear breakdown

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Abstract
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.