Cell cycle control by ataxia telangiectasia mutated protein through regulating retinoblastoma protein phosphorylation

Abstract

The ability of cells to maintain their genomic integrity is essential to the prevention of cancer development. Double-strand breaks (DSBs), the most harmful type of lesion to DNA, are sensed by ataxia-telangiectasia mutated (ATM) protein in association with the MRE11-RAD50-NBS1 complex. The ATM kinase, which is mutated in ataxia-telangiectasia disorder, is a crucial guardian of genomic integrity. Its activation in response to DSBs orchestrates the DNA damage response (DDR) by phosphorylating a plethora of substrates that modulate processes such as DNA repair and cell cycle checkpoints. In this chapter we focus on the molecular mechanisms involved in ATM activation and cell cycle control in response to DSBs and, specifically, on the cross-talk between ATM and retinoblastoma protein (pRb) phosphorylation.