The role of NBS1 in DNA double strand break repair, telomere stability, and cell cycle checkpoint control.
The genomes of eukaryotic cells are under continuous assault by environmental agents and endogenous metabolic byproducts. Damage induced in DNA usually leads to a cascade of cellular events, the DNA damage response. Failure of the DNA damage response can lead to development of malignancy by reducing the efficiency and fidelity of DNA repair. The NBS1 protein is a component of the MRE11/RAD50/NBS1 complex (MRN) that plays a critical role in the cellular response to DNA damage and the maintenance of chromosomal integrity. Mutations in the NBS1 gene are responsible for Nijmegen breakage syndrome (NBS), a hereditary disorder that imparts an increased predisposition to development of malignancy. The phenotypic characteristics of cells isolated from NBS patients point to a deficiency in the repair of DNA double strand breaks. Here, we review the current knowledge of the role of NBS1 in the DNA damage response. Emphasis is placed on the role of NBS1 in the DNA double strand repair, modulation of the DNA damage sensing and signaling, cell cycle checkpoint control and maintenance of telomere stability.
Zhang
Ying
Y
Department of Environmental and Radiological Health Science, Colorado State University, Fort Collins, 80523, USA. Ying.Zhang@colostate.edu
Zhou
Junqing
J
Lim
Chang Uk
CU
D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology*; D043171:Chromosomal Instability; D004249:DNA Damage; D004260:DNA Repair; D018816:Genes, cdc; D006801:Humans; D008954:Models, Biological; D009687:Nuclear Proteins / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000502:physiology*
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D029701:Saccharomyces cerevisiae Proteins; C112156:NBN protein, human