DCLK1 and DNA Damage Response

Abstract

Genome integrity is constantly monitored by sophisticated cellular networks, collectively termed as the DNA damage response (DDR). The DDR is a signaling network that includes cell cycle checkpoints and DNA repair and damage tolerance pathways. Failure of the DDR or associated events causes various diseases, including cancer. DDR is primarily mediated by phosphatidylinositol-3-kinase-like protein kinase (PIKKs) family members ataxia-telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related protein (ATR). However, one of the many unanswered questions regarding these signal-transduction pathways is: how does the cell turn the DDR signals on? There was no conclusive demonstration of the involvement of a specific sensory kinase in DDR signals until our recent research on the DCLK1 role in regulating ATM after genotoxic injury. Currently, various studies are demonstrating the importance of DCLK1 in DNA damage response. Here, we discuss the novel insights into the role of DCLK1 in DNA damage response.

Chronic exposure of humans to high level natural background radiation leads to robust expression of protective stress response proteins

“…DCLK1, MAST2, MAST3 and MAST4) also showed increased abundance in Group II and Group III individuals. Recent reports have emphasized critical role of DCLK1 in DDR and its potential as a radiation mitigator in radiotherapy 37 . The protein DPTOR, a negative regulator of mTOR kinase activity, was one of the very few proteins that were down-regulated in Group II individuals.…”