Ku (protein)
Encyclopedia
Ku is a protein that binds to DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 double-strand break ends
DNA end
DNA end or sticky end refers to the properties of the end of a molecule of DNA or a recombinant DNA molecule. The concept is important in molecular biology, especially in cloning or when subcloning inserts DNA into vector DNA. All the terms can also be used in reference to RNA. The sticky ends or...

 and is required for the non-homologous end joining
Non-homologous end joining
Non-homologous end joining is a pathway that repairs double-strand breaks in DNA. NHEJ is referred to as "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homologous recombination, which requires a homologous sequence to guide...

 (NHEJ) pathway of DNA repair
DNA repair
DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...

. Ku is evolutionarily conserved from bacteria to human. The ancestral bacterial Ku is a homodimer (two copies of the same protein bound to each other). Eukaryotic Ku is a heterodimer of two polypeptides, Ku70 (XRCC6) and Ku80 (XRCC5), so named because the molecular weight of the human Ku proteins is around 70 kDa and 80 kDa. The two Ku subunits form a basket-shaped structure that threads onto the DNA end
DNA end
DNA end or sticky end refers to the properties of the end of a molecule of DNA or a recombinant DNA molecule. The concept is important in molecular biology, especially in cloning or when subcloning inserts DNA into vector DNA. All the terms can also be used in reference to RNA. The sticky ends or...

. Once bound, Ku can slide down the DNA strand, allowing more Ku molecules to thread onto the end. In higher eukaryotes, Ku forms a complex with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to form the full DNA-dependent protein kinase
Protein kinase
A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins...

, DNA-PK. Ku is thought to function as a molecular scaffold to which other proteins involved in NHEJ can bind.

Both subunits of Ku have been experimentally knocked out in mice
Knockout mouse
A knockout mouse is a genetically engineered mouse in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA...

. These mice exhibit chromosomal instability
Chromosome abnormalities
A chromosome anomaly, abnormality or aberration reflects an atypical number of chromosomes or a structural abnormality in one or more chromosomes. A Karyotype refers to a full set of chromosomes from an individual which can be compared to a "normal" Karyotype for the species via genetic testing. A...

, indicating that NHEJ is important for genome maintenance.

In many organisms, Ku has additional functions at telomeres in addition to its role in DNA repair.

Abundance of Ku80 seems to be related to species longevity.
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