Base excision repair is initiated by DNA glycosylases that recognize specific 
altered bases. DNA glycosylases for oxidized bases carry both a glycosylase 
activity that removes the faulty base and an apyrimidinic/apurinic lyase 
activity that introduces a single-strand DNA incision. In particular, the CUT 
domains within the CUX1 and CUX2 proteins were recently shown to interact with 
the 8-oxoguanine (8-oxoG) DNA glycosylase and stimulate its enzymatic 
activities. SATB1, which contains two CUT domains, was originally characterized 
as a T cell-specific genome organizer whose aberrant overexpression in breast 
cancer can promote tumor progression. Here we investigated the involvement of 
SATB1 in DNA repair. SATB1 knockdown caused a delay in DNA repair following 
exposure to H2O2, an increase in OGG1-sensitive oxidized bases within genomic 
DNA, and a decrease in 8-oxoG cleavage activity in cell extracts. In parallel, 
we observed an increase in phospho-CHK1 and γ-H2AX levels and a decrease in DNA 
synthesis. Conversely, ectopic expression of SATB1 accelerated DNA repair and 
reduced the levels of oxidized bases in genomic DNA. Moreover, an enhanced 
GFP-SATB1 fusion protein was rapidly recruited to laser microirradiation-induced 
DNA damage. Using purified proteins, we showed that SATB1 interacts directly 
with OGG1, increases its binding to 8-oxoG-containing DNA, promotes Schiff base 
formation, and stimulates its glycosylase and apyrimidinic/apurinic lyase 
enzymatic activities. Structure/function analysis demonstrated that CUT domains, 
but not the homeodomain, are responsible for the stimulation of OGG1. Together, 
these results identify another CUT domain protein that functions both as a 
transcription factor and an accessory factor in base excision repair.