Evidence for extrinsic exonucleolytic proofreading

Exonucleolytic proofreading of DNA synthesis errors is one of the major determinants of genome stability. However, many DNA transactions that contribute to genome stability require synthesis by polymerases that naturally lack intrinsic 3′ exonuclease activity and some of which are highly inaccurate. Here we discuss evidence that errors made by these polymerases may be edited by a separate 3′ exonuclease, and we consider how such extrinsic proofreading may differ from proofreading by exonucleases that are intrinsic to replicative DNA polymerases.