Disruption of PCNA-lamins A/C interactions by prelamin A induces DNA replication fork stalling.

ABSTRACT: The accumulation of prelamin A is linked to disruption of cellular homeostasis, tissue degeneration and aging. Its expression is implicated in compromised genome stability and increased levels of DNA damage, but to date there is no complete explanation for how prelamin A exerts its toxic effects. As the nuclear lamina is important for DNA replication we wanted to investigate the relationship between prelamin A expression and DNA replication fork stability. In this study we report that the expression of prelamin A in U2OS cells induced both mono-ubiquitination of proliferating cell nuclear antigen (PCNA) and subsequent induction of Pol η, two hallmarks of DNA replication fork stalling. Immunofluorescence microscopy revealed that cells expressing prelamin A presented with high levels of colo

SUBMITTER: Cobb AM 

PROVIDER: S-EPMC5120601 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature