Jc. Chao et al., INTRACELLULAR-DISTRIBUTION OF HMG1, HMG2 AND UBF CHANGE FOLLOWING TREATMENT WITH CISPLATIN, Biochimica et biophysica acta, N. Gene structure and expression, 1307(2), 1996, pp. 213-219
Cisplatin (CDDP) is a widely used cancer chemotherapeutic agent. CDDP
forms well characterized intrastrand cross-links between adjacent puri
nes in genomic DNA. In mammalian cells, these lesions are repaired by
the nucleotide excision repair system. An early event in the recogniti
on and processing of cis-Pt-DNA adducts may well involve the binding o
f specific proteins to the sites of damage. Several proteins have been
identified, including high mobility group (HMG) proteins 1 and 2 and
upstream binding factor (UBF), which recognize CDDP-DNA. However, the
physiological significance of this binding has not been established. I
n this study, we have utilized antibodies to these proteins to examine
the effect of CDDP on their intracellular distribution. Marked change
s in the immunofluorescent staining pattern of HMG1/HMG2 were noted in
cells treated with CDDP. At higher drug concentrations, the distribut
ion of UBF also changed, from a clustered appearance associated with t
he nucleoli to more diffuse nuclear staining, These results demonstrat
e that HMG1/HMG2 and UBF respond to drug treatment, presumably by reco
gnizing cis-Pt-DNA adduct formation in intact cells. Hence, these prot
eins may play an important role in directing the response of tumor cel
ls following exposure to CDDP.