Reference: Taylor MRG and Yeeles JTP (2019) Dynamics of Replication Fork Progression Following Helicase-Polymerase Uncoupling in Eukaryotes. J Mol Biol 431(10):2040-2049

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Abstract


Leading-strand polymerase stalling at DNA damage impairs replication fork progression. Using biochemical approaches, we show this arises due to both slower template unwinding following helicase-polymerase uncoupling and establishment of prolonged stalled fork structures. Fork slowing and stalling occur at structurally distinct lesions, are always associated with continued lagging-strand synthesis, are observed when either Pol ε or Pol δ stalls at leading-strand damage, and do not require specific helicase-polymerase coupling factors. Hence, the key trigger for these replisome-intrinsic responses is cessation of leading-strand polymerization, revealing this as a crucial driver of normal replication fork rates. We propose that this helps balance the need for sufficient uncoupling to activate the DNA replication checkpoint with excessive destabilizing single-stranded DNA exposure in eukaryotes.

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Journal Article | Research Support, Non-U.S. Gov't
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Taylor MRG, Yeeles JTP
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