Apoptotic Effectors in DNA Damage Response

The conclusion that p53 can either cause cell-cycle arrest or apoptosis in response to DNA damage is without dispute. However, we have not completely elucidated the rules that govern the selection of these two cell fates (Oren, 2003). There is emerging evidence to indicate p53 can selectively bind to different promoters, depending on the status of its 

Rad51 (Yuan et al, 1998), Rad52 (Kitao and Yuan, 2002), and UV-DDB2 (Cong et al, 2002). The effects of these tyrosine phosphorylation events on DNA repair, cell-cycle checkpoints, or cell death are not understood. 

the MRE11-RAD50-NBS1 complex appears to play multiple roles, including lesion detection, DNA repair, and signal transduction. 

The notion that lesion-binding proteins can function as sensors of DNA damage to activate downstream signal transduction pathways is gaining support but is far from proven. Further investigation is required to directly link Mismatch Repair, UV-DDB, MRN, or other repair proteins to the activation of checkpoints or apoptosis. 

Alternative Models for the Temporal Coordination of DNA Damage Responses 

---