Structural basis for coupled DNA replication and uracil repair by a family of DNA polymerases from phages with T-modified genomes.

Cryo-EM structures of fused A-family DNA polymerases with an active UDG domain from phages (YerA41 and phiLo) show dU recognition ahead of the replication fork and preferential bypass via dA incorporation.

• Why it matters: Phage genomes often encode UDG separately or within DNAPs, but the structural mechanism for coupling uracil repair to replication—while preserving genome integrity—remains unclear.
• What they did: The authors determined atomic cryo-EM structures in multiple active functional and conformational states for two phage members, and also analyzed genomes containing both an X-family DNAP and a DNA ligase.
• The result: The UDG domain generates abasic sites from dU that are preferentially bypassed through dA incorporation, and co-occurring X-family DNAP and ligase suggest replication-coupled base excision repair executed on-the-fly.