Unscheduled DNA replication in G1 causes genome instability and damage signatures indicative of replication collisions.

ABSTRACT: DNA replicates once per cell cycle. Interfering with the regulation of DNA replication initiation generates genome instability through over-replication and has been linked to early stages of cancer development. Here, we engineer genetic systems in budding yeast to induce unscheduled replication in a G1-like cell cycle state. Unscheduled G1 replication initiates at canonical S-phase origins. We quantifiy the composition of replisomes in G1- and S-phase and identified firing factors, polymerase α, and histone supply as factors that limit replication outside S-phase. G1 replication per se does not trigger cellular checkpoints. Subsequent replication during S-phase, however, results in over-replication and leads to chromosome breaks and chromosome-wide, strand-biased occurrence of RPA-bound si

SUBMITTER: Reusswig KU 

PROVIDER: S-EPMC9674678 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature