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Dynamics of leading-strand lesion skipping by the replisome.

ABSTRACT: The E. coli replisome stalls transiently when it encounters a lesion in the leading-strand template, skipping over the damage by reinitiating replication at a new primer synthesized downstream by the primase. We report here that template unwinding and lagging-strand synthesis continue downstream of the lesion at a reduced rate after replisome stalling, that one replisome is capable of skipping multiple lesions, and that the rate-limiting steps of replication restart involve the synthesis and activation of the new primer downstream. We also find little support for the concept that polymerase uncoupling, where extensive lagging-strand synthesis proceeds downstream in the absence of leading-strand synthesis, involves physical separation of the leading-strand polymerase from the replisome. Instead, our data indicate that extensive uncoupled replication likely results from a failure of the leading-strand polymerase still associated with the DNA helicase and the lagging-strand polymerase that are proceeding downstream to reinitiate synthesis.

SUBMITTER: Yeeles JT

PROVIDER: S-EPMC3877186 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Dynamics of leading-strand lesion skipping by the replisome.

Yeeles Joseph T P JT Marians Kenneth J KJ

Molecular cell 20131121 6

The E. coli replisome stalls transiently when it encounters a lesion in the leading-strand template, skipping over the damage by reinitiating replication at a new primer synthesized downstream by the primase. We report here that template unwinding and lagging-strand synthesis continue downstream of the lesion at a reduced rate after replisome stalling, that one replisome is capable of skipping multiple lesions, and that the rate-limiting steps of replication restart involve the synthesis and act ...[more]

PMID: 24268579

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