SEQUENCE-DEPENDENT ALKYLATION OF GUANINE RESIDUES IN DUPLEX DNA - MOLECULAR-DYNAMICS STUDY

We present data to explain the sequence dependence of alkylation at th e O-6 position of guanine. Both methylation and ethylation of O-6-guan ine occur at either the first or the second position of the middle cod on, GGA, in the DNA double helix d(5'-GGCGCTGGAGGCGTG-3'). From our mo lecular dynamics studies, parameters such as hydrogen bonding, surface accessibility and root-mean-square deviation, provide an atomic ratio nale for the fact that the second guanine of the middle codon of the s equence is the preferred site for alkylation in this sequence. Further more, the recognition and repair by O-6-alkylguanine-DNA alkyl transfe rase (AGT) is less effective for alkylation at the second position tha n the first, and is also less effective for O-6-ethylguanine (O-6-etG) than for O-6-methylguanine (O-6-meG).