Txt. Sayle et Jm. Goodfellow, SEQUENCE-DEPENDENT ALKYLATION OF GUANINE RESIDUES IN DUPLEX DNA - MOLECULAR-DYNAMICS STUDY, Journal of the Chemical Society. Faraday transactions, 93(14), 1997, pp. 2413-2418
Citations number
41
Categorie Soggetti
Chemistry Physical","Physics, Atomic, Molecular & Chemical
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).