Chlorambucil Cytotoxicity in Malignant B Lymphocytes Is Synergistically Increased by 2-(Morpholin-4-yl)-benzo[h]chomen-4-one (NU7026)-Mediated Inhibition of DNA Double-Strand Break Repair via Inhibition of DNA-Dependent Protein Kinase

2007 ◽  
Vol 321 (3) ◽  
pp. 848-855 ◽  
Author(s):  
Lilian Amrein ◽  
Martin Loignon ◽  
Anne-Christine Goulet ◽  
Michael Dunn ◽  
Bertrand Jean-Claude ◽  
...  
1996 ◽  
Vol 351 (1336) ◽  
pp. 173-179 ◽  

DNA-dependent protein kinase is a nuclear serine/threonine kinase whose catalytic properties are expressed only when the enzyme is bound to DNA ends or other discontinuities in the DNA. DNA-PK comprises two components: one mediates binding to DNA and corresponds to the heterodimeric human autoimmune antigen Ku; the other, DNA-PK catalytic subunit (DNA-PKCS), is a polypeptide of approximately 450 kDa. DNA-PK deficiencies are associated with certain mutant rodent cell lines that display defects in DNA double strand break repair and V(D)J recombination. Specifically, hamster xrs- 6 cells lack Ku function, whereas murine scid and hamster V3 cells lack functional DNA-PKCS. Furthermore, the phenotypes of xrs-6 and V3 cells can be corrected by the expression of the genes encoding the 80 kDa component of Ku or DNA-PKCS, respectively. These results imply that DNA-PK is an important component of the DNA double strand break repair/recombination apparatus. Possible roles for DNA-PK in these processes are discussed.


Aging ◽  
2009 ◽  
Vol 1 (1) ◽  
pp. 109-121 ◽  
Author(s):  
Ronald A. McCord ◽  
Eriko Michishita ◽  
Tao Hong ◽  
Elisabeth Berber ◽  
Lisa D. Boxer ◽  
...  

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