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Gene repair and Ku80

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by: Larry Reid
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Word Count: 340

Ku is an abundant heterodimeric nuclear protein composed of the two dimers Ku70 and Ku80. Encoded by the XRCC5 gene, they play an essential role in DNA repair; Ku80 antibodies are used in a range of studies, including cancer research. We at Novus Biologicals have over 55 Ku80 products in our antibody catalogue.

The Ku heterodimer plays a number of roles in DNA repair, initiating the NHEJ (non-homologous end joining) repair pathway for double-end breaks as well as repairing nicks, gaps and hairpins. Ku also promotes antigen diversity in the immune system, via V(D)J recombination. It was first identified in lupus patients, who were found to have high levels of antibodies to the Ku autoantigen.

Other roles include cell signalling, transcriptional activation, DNA replication, subtelomeric gene silencing, telomere length maintenance and apoptosis. However, its most important function is the repair of double-strand breaks.

Numerous studies have shown the role that DNA damage plays in age-related diseases, including cancer. Damage is caused by numerous factors including environment, lifestyle and the aging process itself. The body has a great number of repair pathways to counteract this, but the exact mechanisms are often ill understood.

Ku initiates DNA repair by becoming a subunit of DNA-PK (DNA-dependent protein kinase), targeting it to the DNA damage site. The Ku/DNA-PK complex has been suggested to play a structural role, maintaining the structure via a framework so the ends of the broken chromosomes are held together while repair takes place.

Recently, researchers at the University of North Carolina discovered exciting new evidence which suggests Ku repairs breaks at a much more fundamental level. One of the most serious forms of DNA damage, double-end breaks can occur in more than one place, leaving the chromosome resembling frayed yarn. It appears that Ku actually “clans up” these frayed ends, repairing the strand at individual nucleotides to initiate fast “healing.”

Antibody suppliers use studies of this kind as a key to expanding their antibody databases, enabling even more ground-breaking discoveries to take place.
 

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