Upregulation of Mcl-1S Causes Cell-Cycle Perturbations and DNA Damage Accumulation

Cell cycle arrest at the initiation step of human chromosomal DNA replication causes DNA damage.

Cell cycle arrest in response to environmental effects can lead to DNA breaks. We investigated whether inhibition of DNA replication during the initiation step can lead to DNA damage and characterised a cell-cycle-arrest point at the replication initiation step before the establishment of active replication forks. This arrest can be elicited by the iron chelators mimosine, ciclopirox olamine or...

DNA-dependent protein kinase is not required for accumulation of p53 or cell cycle arrest after DNA damage.

In response to DNA damage, cells transduce a signal that leads to accumulation and activation of p53 protein, transcriptional induction of several genes, including p21, gadd45, and gadd153, and cell cycle arrest. One hypothesis is that the signal is mediated by DNA-dependent protein kinase (DNA-PK), which consists of a catalytic subunit (DNA-PKcs) and a regulatory subunit (Ku). DNA-PK has sever...

Cell Cycle and DNA Damage Response in Postmitotic Neurons

Centrosomal Chk2 in DNA damage responses and cell cycle progression.

Two major control systems regulate early stages of mitosis: activation of Cdk1 and anaphase control through assembly and disassembly of the mitotic spindle. In parallel to cell cycle progression, centrosomal duplication is regulated through proteins including Nek2. Recent studies suggest that centrosome-localized Chk1 forestalls premature activation of centrosomal Cdc25b and Cdk1 for mitotic en...

Linking cell cycle reentry and DNA damage in neurodegeneration.

Aberrant cell cycle activity and DNA damage have been observed in neurons in association with various neurodegenerative conditions. While there is strong evidence for a causative role for these events in neurotoxicity, it is unclear how they are triggered and why they are toxic. Here, we introduce a brief background of the current view on cell cycle activity and DNA damage in neurons and specul...