Protein recognition of the S23906-1{-}DNA adduct by nuclear proteins: direct involvement of glyceraldehyde-3-phosphate-dehydrogenase (GAPDH)

The objective of this study is to identify proteins involved in the recognition and mechanism of action of S23906-DNA adducts. We found glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) as a protein that binds to S23906-alkylated single-, double-stranded and telomeric sequences in a drug-dependant and DNA sequence/structure-dependant manner. We used cyclic amplification of sequence targeting (CASTing) method to identify GAPDH DNA-binding selectivity and then evaluate its binding to such selected S23906-alkylated sequences. At the cellular level, alkylation of S23906-1 results in an increase of the binding of GAPDH and its protein partner HMG-B1 to the chromatin. Regarding the multiple roles of GAPDH in apoptosis and DNA repair, cytotoxic and apoptotic activities of GAPDH were evaluated and present opposite effect in two different cellular models.
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Cell Source Type: research