3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells.

ABSTRACT: In mammalian cells, chromosomal replication starts at thousands of origins at which replisomes are assembled. Replicative stress triggers additional initiation events from 'dormant' origins whose genomic distribution and regulation are not well understood. In this study, we have analyzed origin activity in mouse embryonic stem cells in the absence or presence of mild replicative stress induced by aphidicolin, a DNA polymerase inhibitor, or by deregulation of origin licensing factor CDC6. In both cases, we observe that the majority of stress-responsive origins are also active in a small fraction of the cell population in a normal S phase, and stress increases their frequency of activation. In a search for the molecular determinants of origin efficiency, we compared the genetic and epigeneti

SUBMITTER: Jodkowska K 

PROVIDER: S-EPMC9757045 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature