Paper Info
Title
Replication pauses of the wild-type and mutant mitochondrial DNA polymerase gamma: a simulation study.
Abstract
The activity of polymerase gamma is complicated, involving both correct and incorrect DNA polymerization events, exonuclease activity, and the disassociation of the polymerase: DNA complex. Pausing of pol-gamma might increase the chance of deletion and depletion of mitochondrial DNA. We have developed a stochastic simulation of pol-gamma that models its activities on the level of individual nucleotides for the replication of mtDNA. This method gives us insights into the pausing of two pol-gamma variants: the A467T substitution that causes PEO and Alpers syndrome, and the exonuclease deficient pol-gamma (exo(-)) in premature aging mouse models. To measure the pausing, we analyzed simulation results for the longest time for the polymerase to move forward one nucleotide along the DNA strand. Our model of the exo(-) polymerase had extremely long pauses, with a 30 to 300-fold increase in the time required for the longest single forward step compared to the wild-type, while the naturally occurring A467T variant showed at most a doubling in the length of the pauses compared to the wild-type. We identified the cause of these differences in the polymerase pausing time to be the number of disassociations occurring in each forward step of the polymerase.
Year
DOI
Venue
2011
10.1371/journal.pcbi.1002287
PLOS COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
mutation,nucleotides,computational biology,dna replication,stochastic processes,stochastic simulation,wild type,computer simulation,mitochondrial dna
Biology,DNA polymerase delta,DNA polymerase II,Polymerase,Exonuclease,Bioinformatics,DNA replication,Genetics,Molecular biology,DNA polymerase,DNA clamp,Premature aging
Journal
Volume
Issue
ISSN
7
11
1553-734X
Citations 
PageRank 
References 
0
0.34
1
Authors
3
Name
Order
Citations
PageRank
Zhuo Song132.10
Yang Cao2519.23
David C. Samuels3186.68