The Mechanism of Replication Stalling and Recovery within Repetitive DNA

• DOI: 10.1101/2021.06.02.446729
• Publication Date: 2021-06-03T01:20:22Z
• Authors: Corella S Casas-D...; Manuel Daza-Martin; Sophie L Williams; Gideon Coster
• Keywords: Replisome; Origin recognition complex; Minichromosome maintenance; Pre-replication complex; Semiconservative replication; Replication factor C; Licensing factor

SUMMARY Accurate chromosomal DNA replication is essential to maintain genomic stability. Genetic evidence suggests that certain repetitive sequences impair replication, yet the underlying mechanism poorly defined. Replication could be directly inhibited by template or indirectly, for example DNA-bound proteins. Here, we reconstituted of mono-, di- and trinucleotide repeats in vitro using eukaryotic replisomes assembled from purified We found structure-prone are sufficient replication. Whilst unwinding was unaffected, leading strand synthesis inhibited, fork uncoupling. Synthesis through hairpin-forming relied on replisome-intrinsic mechanisms, whereas quadruplex-forming required an extrinsic accessory helicase. DNA-induced stalling mechanistically similar induced lesions, highlighting as important potential source stress. Thus, propose our understanding cellular response stress also applies sequences.