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DNA annealing helicase and endonuclease ZRANB3 is a structure-specific, ATP-dependent enzyme belonging to the SNF2-family of ATPases, with both helicase and HNH endonuclease activities[1][2][3][4]. ZRANB3 is crucial for resolving replication stress by processing branched DNA structures and stalled replication forks, being recruited to these sites via interactions with polyubiquitinated PCNA and branched DNA. It aids DNA repair and genome stability by cleaving replication fork intermediates and catalyzing fork regression, thus preventing fork collapse and limiting inappropriate recombination[1][2][3][4]. ZRANB3 contains an N-terminal helicase domain, a PIP box and APIM motif (for PCNA binding), an Npl4-type zinc finger, and a C-terminal HNH endonuclease domain[3]. Mutational disruption may predispose to cancer and other diseases associated with genome instability, but direct therapeutic targeting is not yet established.
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