ATR-mediated regulation of nuclear and cellular plasticity.
ATR (Ataxia Telangiectasia and Rad3-related) is a member of the Phosphatidylinositol 3-kinase-related kinases (PIKKs) family, amongst six other vertebrate proteins known so far. ATR is indispensable for cell survival and its essential role is in sensing DNA damage and initiating appropriate repair responses. In this review we highlight emerging and recent observations connecting ATR to alternative roles in controlling the nuclear envelope, nucleolus, centrosome and other organelles in response to both internal and external stress conditions. We propose that ATR functions control cell plasticity by sensing structural deformations of different cellular components, including DNA and initiating appropriate repair responses, most of which are yet to be understood completely.
Istituto FIRC di Oncologia Molecolare, Milan, Italy; University of Milan, Milan, Italy.
Gururaj Rao
GR
Kidiyoor
Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, M.G. Marg, Lucknow 226001, India; Academy of Scientific and Innovative Research (AcSIR), India.
Amit
A
Kumar
Istituto FIRC di Oncologia Molecolare, Milan, Italy; University of Milan, Milan, Italy. Electronic address: marco.foiani@ifom-ieo-campus.it.
Marco
M
Foiani
D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism; D002466:Cell Nucleolus / Q000378:metabolism / Q000648:ultrastructure; D000066670:Cell Plasticity; D018385:Centrosome / Q000378:metabolism / Q000648:ultrastructure; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D005057:Eukaryotic Cells / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D009685:Nuclear Envelope / Q000378:metabolism / Q000648:ultrastructure
D004247:DNA; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
ATR; Cellular plasticity; Centrosome; Nuclear envelope; Nucleolus; PIKK