PT  - JOURNAL ARTICLE
AU  - Halim, Vincentius A.
AU  - Alvarez-Fernández, Mónica
AU  - Xu, Yan Juan
AU  - Aprelia, Melinda
AU  - van den Toorn, Henk W. P.
AU  - Heck, Albert J. R.
AU  - Mohammed, Shabaz
AU  - Medema, René H.
TI  - Comparative Phosphoproteomic Analysis of Checkpoint Recovery Identifies New Regulators of the DNA Damage Response
AID  - 10.1126/scisignal.2003664
DP  - 2013 Apr 23
TA  - Science Signaling
PG  - rs9--rs9
VI  - 6
IP  - 272
4099  - http://stke.sciencemag.org/content/6/272/rs9.short
4100  - http://stke.sciencemag.org/content/6/272/rs9.full
SO  - Sci. Signal.2013 Apr 23; 6
AB  - How cells recover from a DNA damage–induced arrest is currently poorly understood. We performed large-scale quantitative phosphoproteomics to identify changes in protein phosphorylation that occurred during recovery from arrest in the G2 phase of the cell cycle caused by DNA damage. We identified 154 proteins that were differentially phosphorylated, and systematic depletion of each of these differentially phosphorylated proteins by small interfering RNA (siRNA) identified at least 10 potential regulators of recovery. Astrin, a protein associated with the mitotic spindle, was among the potential regulators of recovery. We found that astrin controlled the abundance of the cell cycle regulator p53 during DNA damage–induced arrest. Cells in which astrin was depleted had decreased murine double minute 2 (MDM2) abundance and increased p53 at the later stages of the DNA damage response. Astrin was required for continued expression of genes encoding proteins that promote cell cycle progression in arrested cells. Thus, by controlling p53 abundance in cells recovering from DNA damage, astrin maintains the cells in a state competent to resume the cell cycle.