当前位置： SCI文献检索 > PLoS Genetics期刊下所有文献 > Mismatch repair balances leading and lagging strand DNA replication fidelity.

Mismatch repair balances leading and lagging strand DNA replication fidelity.

Abstract：

:The two DNA strands of the nuclear genome are replicated asymmetrically using three DNA polymerases, α, δ, and ε. Current evidence suggests that DNA polymerase ε (Pol ε) is the primary leading strand replicase, whereas Pols α and δ primarily perform lagging strand replication. The fact that these polymerases differ in fidelity and error specificity is interesting in light of the fact that the stability of the nuclear genome depends in part on the ability of mismatch repair (MMR) to correct different mismatches generated in different contexts during replication. Here we provide the first comparison, to our knowledge, of the efficiency of MMR of leading and lagging strand replication errors. We first use the strand-biased ribonucleotide incorporation propensity of a Pol ε mutator variant to confirm that Pol ε is the primary leading strand replicase in Saccharomyces cerevisiae. We then use polymerase-specific error signatures to show that MMR efficiency in vivo strongly depends on the polymerase, the mismatch composition, and the location of the mismatch. An extreme case of variation by location is a T-T mismatch that is refractory to MMR. This mismatch is flanked by an AT-rich triplet repeat sequence that, when interrupted, restores MMR to > 95% efficiency. Thus this natural DNA sequence suppresses MMR, placing a nearby base pair at high risk of mutation due to leading strand replication infidelity. We find that, overall, MMR most efficiently corrects the most potentially deleterious errors (indels) and then the most common substitution mismatches. In combination with earlier studies, the results suggest that significant differences exist in the generation and repair of Pol α, δ, and ε replication errors, but in a generally complementary manner that results in high-fidelity replication of both DNA strands of the yeast nuclear genome.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Lujan SA,Williams JS,Pursell ZF,Abdulovic-Cui AA,Clark AB,Nick McElhinny SA,Kunkel TA

doi

10.1371/journal.pgen.1003016

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

e1003016

issue

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-12-00710

journal_volume

pub_type

杂志文章

在线工具

Mismatch repair balances leading and lagging strand DNA replication fidelity.