AUTHOR=Castillo-Lizardo Melissa , Henneke Ghislaine , Viguera Enrique 

TITLE=Replication slippage of the thermophilic DNA polymerases B and D from the Euryarchaeota Pyrococcus abyssi

JOURNAL=Frontiers in Microbiology

VOLUME=5

YEAR=2014

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2014.00403

DOI=10.3389/fmicb.2014.00403

ISSN=1664-302X

ABSTRACT=<p>Replication slippage or slipped-strand mispairing involves the misalignment of DNA strands during the replication of repeated DNA sequences, and can lead to genetic rearrangements such as microsatellite instability. Here, we show that PolB and PolD replicative DNA polymerases from the archaeal model <italic>Pyrococcus abyssi</italic> (<italic>Pab</italic>) slip <italic>in vitro</italic> during replication of a single-stranded DNA template carrying a hairpin structure and short direct repeats. We find that this occurs in both their wild-type (exo+) and exonuclease deficient (exo-) forms. The slippage behavior of <italic>Pab</italic>PolB and <italic>Pab</italic>PolD, probably due to limited strand displacement activity, resembles that observed for the high fidelity <italic>P. furiosus</italic> (<italic>Pfu</italic>) DNA polymerase. The presence of <italic>Pab</italic>PCNA inhibited <italic>Pab</italic>PolB and <italic>Pab</italic>PolD slippage. We propose a model whereby <italic>Pab</italic>PCNA stimulates strand displacement activity and polymerase progression through the hairpin, thus permitting the error-free replication of repetitive sequences.</p>