Document Detail


Changes in the level and distribution of Ku proteins during cellular senescence.
MedLine Citation:
PMID:  17686666     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Aging is associated with accumulation of genomic rearrangements consistent with aberrant repair of DNA breaks. We have shown previously that DNA repair by non-homologous end joining (NHEJ) becomes less efficient and more error-prone in senescent cells. Here, we show that the levels of Ku70 and Ku80 drop approximately twofold in replicatively senescent cells. Intracellular distribution of Ku also changes. In the young cells roughly half of Ku is located in the nucleus and half in the cytoplasm. In senescent cells the nuclear levels of Ku do not change, while the cytoplasmic Ku fraction disappears. Upon treatment with gamma-irradiation, in the young cells cytoplasmic Ku moved into the nuclear and membrane fractions, while no change in the Ku distribution occurred in senescent cells. Upon treatment with UVC Ku moved out of the nucleus in the young cells, while most Ku remained nuclear in senescent cells. This suggests that the nuclear Ku in senescent cells is unable to respond to DNA damage. We hypothesize that overall decline in Ku levels changes in Ku intracellular distribution, and the loss of appropriate response of Ku to DNA damage in senescent cells contribute to the decline of NHEJ and to age-related genomic instability.
Authors:
Andrei Seluanov; Jacquelynn Danek; Nola Hause; Vera Gorbunova
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-08-07
Journal Detail:
Title:  DNA repair     Volume:  6     ISSN:  1568-7864     ISO Abbreviation:  DNA Repair (Amst.)     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-11-12     Completed Date:  2008-02-05     Revised Date:  2014-09-10    
Medline Journal Info:
Nlm Unique ID:  101139138     Medline TA:  DNA Repair (Amst)     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1740-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Antigens, Nuclear / metabolism*
Blotting, Western
Cell Aging*
DNA Damage
DNA-Binding Proteins / metabolism*
Humans
Immunohistochemistry
Subcellular Fractions / metabolism
Grant Support
ID/Acronym/Agency:
AG027237/AG/NIA NIH HHS; R01 AG027237/AG/NIA NIH HHS; R01 AG027237-01A1/AG/NIA NIH HHS; R01 AG027237-02/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Nuclear; 0/DNA-Binding Proteins; 0/Ku autoantigen
Comments/Corrections

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