title: The role of NBS1 in the modulation of PIKK family proteins ATM and ATR in the cellular response to DNA damage.
abstract: Ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) kinases have been considered the primary activators of the cellular response to DNA damage. They belong to the protein kinase family, phosphoinositide 3-kinase-related kinase (PIKKs). In human beings, deficiency of these kinases leads to hereditary diseases, namely ataxia telangiectasia (AT) with ATM deficiency and ATR-Seckel with ATR deficiency. NBS1, a component of MRE11/RAD50/NBS1 (MRN) complex, is another important player in DNA damage response (DDR). Mutations of NBS1 are responsible for Nijmegen breakage syndrome (NBS), a human hereditary disease with the characteristics that almost encompassed those of AT and ATR-Seckel. NBS1 has been conventionally thought to be a downstream substrate of ATM and ATR in DDR; however, recent studies suggest that NBS1/MRN functions upstream of both ATM and ATR by recruiting them to the proximity of DNA damage sites and activating their functions. In this mini-review, we would emphasize the requirement of NBS1 as an upstream mediator for the modulation of PIKK family proteins ATM and ATR.
authors.affiliation: Department of Environmental and Radiological Health Science, Colorado State University, Fort Collins, CO 80521, USA.
authors.forename: Junqing
authors.initials: J
authors.lastname: Zhou
authors.forename: Chang Uk
authors.initials: CU
authors.lastname: Lim
authors.forename: Jian Jian
authors.initials: JJ
authors.lastname: Li
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism* / Q000502:physiology*; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009687:Nuclear Proteins / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases