Cytosine unstacking and strand slippage at an insertion-deletion mutation sequence in an overhang-containing DNA duplex.

ABSTRACT: Base unstacking in template strands, when accompanied by strand slippage, can result in deletion mutations during strand extension by nucleic acid polymerases. In a GCCC mutation hot-spot sequence, which was previously identified to have a 50% probability of causing such mutations during DNA replication by a Y-family polymerase, a single-base deletion mutation could result from such unstacking of any one of its three template cytosines. In this study, the intrinsic energetic differences in unstacking among these three cytosines in a solvated DNA duplex overhang model were examined using umbrella sampling molecular dynamics simulations. The free energy profiles obtained show that cytosine unstacking grows progressively more unfavorable as one moves inside the duplex from the 5'-end of the o

SUBMITTER: Manjari SR 

PROVIDER: S-EPMC4063443 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature