Human normal peripheral blood B-lymphocytes are deficient in DNA-dependent protein kinase activity due to the expression of a variant form ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1998-03

AUTHORS

Catherine Muller, Caroline Dusseau, Patrick Calsou, Bernard Salles

ABSTRACT

The heterodimeric Ku protein, which comprises a 86 kDa (Ku86) amd a 70 kDa (Ku70) subunits, is an abundant nuclear DNA-binding protein which binds in vitro to DNA termini without sequence specificity. Ku is the DNA-targeting component of the large catalytic sub-unit of the DNA-dependent protein kinase complex (DNA-PK[CS]), that plays a critical role in mammalian double-strand break repair and lymphoid V(D)J recombination. By using electrophoretic mobility shift assays, we demonstrated that in addition to the major Ku x DNA complex usually detected in cell line extracts, a second complex with faster electrophoretic mobility was observed in normal peripheral blood lymphocytes (PBL) extracts. The presence of this faster migrating complex was restricted to B cells among the circulating lymphocyte population. Western blot analysis revealed that B cells express a variant form of the Ku86 protein with an apparent molecular weight of 69 kDa, and not the 86 kDa- full-length protein. Although the heterodimer Ku70/variant-Ku86 binds to DNA-ends, this altered form of the Ku heterodimer has a decreased ability to recruit the catalytic component of the complex, DNA-PK(CS), which contributes to an absence of detectable DNA-PK activity in B cells. These data provide a molecular basis for the increased sensitivity of B cells to ionizing radiation and identify a new mechanism of regulation of DNA-PK activity that operates in vivo. More... »

PAGES

1553

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1201676

DOI

http://dx.doi.org/10.1038/sj.onc.1201676

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1007726776

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/9569022


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