Elevated poly-(ADP-ribose)-polymerase activity sensitizes retinoblastoma-deficient cells to DNA damage-induced necrosis.

ABSTRACT: The retinoblastoma (Rb) tumor suppressor is a key regulator of cell cycle checkpoints but also protects against cell death induced by stresses such as DNA damage and death receptor ligation. We report here that cell death of Rb-deficient cells exposed to key genotoxic agents was associated with increased expression of S phase-specific E2F target genes and cell death consistently occurred in the S phase of the cell cycle. Cell cycle arrest induced by serum starvation prevented S phase entry, attenuated DNA damage, and promoted survival, suggesting that Rb-null cells die due to a failure to prevent S phase entry. DNA damage-induced death of Rb-null cells was associated with nucleotide depletion, higher activity of poly-ADP-ribose-polymerase (Parp), and cell death that was primarily necrotic.

SUBMITTER: Liu H 

PROVIDER: S-EPMC2994938 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature