Response of the replisome to araA and araC suggests a mechanism for arabinosyl nucleoside tolerance.

Pol δ replaces Pol ε to synthesize and proofread nascent leading strands, mediating tolerance to araA and araC in the eukaryotic replisome.

• Why it matters: Understanding how the replisome responds to ara nucleoside analogues is crucial because these drugs inhibit DNA synthesis and resistance mechanisms impact their clinical effectiveness.
• What they did: The study examined the response of the eukaryotic replisome to araA and araC using in vitro and in vivo experiments, focusing on the roles of DNA polymerases Pol δ and Pol ε.
• The result: Pol δ's activity limits helicase-polymerase uncoupling and intra-S checkpoint activation, suggesting that proofreading and removal of ara analogues by Pol δ may be primary resistance mechanisms.