Dynamic transcriptome profiling in DNA damage-induced cellular senescence and transient cell-cycle arrest

Abstract

Cellular senescence is an irreversible cell cycle arrest process associated with aging and senescence-related diseases. DNA damage is an extensive feature of cellular senescence and aging. Different levels of DNA damage could lead to cellular senescence or transient cell-cycle arrest, but the genetic regulatory mechanisms determining cell fate are still not clear. In this work, high-resolution time course analysis of gene expression in DNA damage-induced cellular senescence and transient cell-cycle arrest was used to explore the transcriptomic differences between different cell fates after DNA damage response and to investigate the key regulatory factors affecting senescent cell fates. Pathways such as the cell cycle, DNA repair and cholesterol metabolism showed characteristic differential response. A number of key transcription factors were predicted to regulating cell cycle and DNA repair. Our study provides genome-wide insights into the molecular-level mechanisms of senescent cell fate decisions after DNA damage response.