The role of NBS1 in the modulation of PIKK family proteins ATM and ATR in the cellular response to DNA damage

Junqing Zhou, Chang UK Lim, Jian-Jian Li, Lu Cai, Ying Zhang

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)9-15
Number of pages7
JournalCancer Letters
Volume243
Issue number1
DOIs
StatePublished - Nov 8 2006
Externally publishedYes

Keywords

  • DNA damage response
  • NBS1
  • PIKK

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Fingerprint Dive into the research topics of 'The role of NBS1 in the modulation of PIKK family proteins ATM and ATR in the cellular response to DNA damage'. Together they form a unique fingerprint.

Cite this