Ku70 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

that, in humans, is encoded by the ''XRCC6''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

Function

Together, Ku70 and

Ku80 Ku80 is a protein that, in humans, is encoded by the ''XRCC5'' gene. Together, Ku70 and Ku80 make up the Ku heterodimer, which binds to DNA double-strand break ends and is required for the non-homologous end joining (NHEJ) pathway of DNA repai ...

make up the Ku heterodimer, which binds to DNA double-strand break ends and is required for the

non-homologous end joining Non-homologous end joining (NHEJ) 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 homology direct ...

(NHEJ) pathway of

DNA repair DNA repair is 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 radiation can cause DNA da ...

. It is also required for

V(D)J recombination V(D)J recombination is the mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. It results in the highly diverse repertoire of antibodies/immunoglobulins and T cell re ...

, which utilizes the NHEJ pathway to promote antigen diversity in the mammalian

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as Tumor immunology, cancer cells and objects such ...

. In addition to its role in NHEJ, Ku is also required for

telomere A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature mo ...

length maintenance and subtelomeric gene silencing. Ku was originally identified when patients with

systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...

were found to have high levels of autoantibodies to the protein.

Aging

Mouse embryonic stem cells with homozygous Ku70 mutations, that is Ku70^−/− cells, have markedly increased sensitivity to ionizing radiation compared to heterozygous Ku70^+/− or wild-type Ku70^+/+ embryonic stem cells. Mutant mice deficient in Ku70 exhibit early aging. Using several specific criteria of aging, the mutant mice were found to display the same aging signs as control mice, but at a considerably earlier chronological age. These results suggest that reduced ability to repair DNA double-strand breaks causes early aging, and that the wild-type Ku70 gene plays an important role in longevity assurance.Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K (2008). Cancer and aging as consequences of un-repaired DNA damage. In: New Research on DNA Damages (Editors: Honoka Kimura and Aoi Suzuki) Nova Science Publishers, Inc., New York, Chapter 1, pp. 1-47. open access, but read only https://www.novapublishers.com/catalog/product_info.php?products_id=43247 (Also see

DNA damage theory of aging The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring DNA damage. Damage in this context is a DNA alteration that has an abnormal structure. Although both mitochondrial and nuclear DN ...

Clinical

A mutation in this gene has been described in a set of 24 families with

autism The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...

. While this is suggestive that this gene may play a role in the development of autism, further investigation is required.

Nomenclature

Ku70 has been referred to by several names including: * Lupus Ku autoantigen protein p70 * ATP-dependent DNA helicase 2 subunit 1 * X-ray repair complementing defective repair in Chinese hamster cells 6 * X-ray repair cross-complementing 6 (XRCC6)

Interactions

Ku70 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizat ...

with: * CBX5, *

CHEK1 Checkpoint kinase 1, commonly referred to as Chk1, is a serine/threonine-specific protein kinase that, in humans, is encoded by the ''CHEK1'' gene. Chk1 coordinates the DNA damage response (DDR) and cell cycle checkpoint response. Activation of Ch ...

, * CREBBP, * GCN5L2, * HOXC4, *

, *

MRE11A Double-strand break repair protein MRE11 is an enzyme that in humans is encoded by the ''MRE11'' gene. The gene has been designated ''MRE11A'' to distinguish it from the pseudogene ''MRE11B'' that is nowadays named ''MRE11P1''. Function This ge ...

, *

NCOA6 Nuclear receptor coactivator 6 is a protein that in humans is encoded by the ''NCOA6'' gene. Function The protein encoded by this gene is a transcriptional coactivator that can interact with nuclear hormone receptors to enhance their transcri ...

, * NCF4, *

PCNA Proliferating cell nuclear antigen (PCNA) is a DNA clamp that acts as a processivity factor for DNA polymerase δ in eukaryotic cells and is essential for replication. PCNA is a homotrimer and achieves its processivity by encircling the DNA, ...

, * PTTG1, *

RPA2 RPA may refer to: Companies * RPA (Rubin Postaer and Associates), advertising agency, Santa Monica, California, US * Republic Airways, ICAO code: RPA Political groups * Republican Party of Arkansas, the affiliate of the Republican Party in Ar ...

, *

TERF2 Telomeric repeat-binding factor 2 is a protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysi ...

, *

TERT Telomerase reverse transcriptase (abbreviated to TERT, or hTERT in humans) is a catalytic subunit of the enzyme telomerase, which, together with the telomerase RNA component (TERC), comprises the most important unit of the telomerase complex. T ...

VAV1 Proto-oncogene vav is a protein that in humans is encoded by the ''VAV1'' gene. Function The protein encoded by this proto-oncogene is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding pr ...

, and * WRN.

References

External links

PDBe-KB
provides an overview of all the structure information available in the PDB for Human X-ray repair cross-complementing protein 6 {{PDB Gallery, geneid=2547