Preservation of lagging strand integrity at sites of stalled replication by Pol α-primase and 9-1-1 complex
Robin van Schendel, Ron Romeijn, Helena Buijs, Marcel Tijsterman
Abstract
genome close to replication-impeding G-quadruplexes, we show that de novo DNA synthesis downstream of the blocked fork suppresses DNA loss. We next identify the pol α-primase complex to limit deletion mutagenesis, a conclusion substantiated by whole-genome analysis of animals carrying mutated POLA2/DIV-1. We subsequently identify a new role for the 9-1-1 checkpoint clamp in protecting Okazaki fragments from resection by EXO1. Together, our results provide a mechanistic model for controlling the fate of replication intermediates at sites of stalled replication.
Topics & Concepts
Replication (statistics)PrimaseLaggingBiologyReplisomeDNA replicationCell biologyGeneticsVirologyDNAMedicineEukaryotic DNA replicationPolymerase chain reactionGeneReverse transcriptasePathologyDNA Repair MechanismsCRISPR and Genetic EngineeringChromosomal and Genetic Variations