In addition to its role in NHEJ, Ku is also required for
telomere length maintenance and subtelomeric gene silencing.[7]
Ku was originally identified when patients with
systemic lupus erythematosus were found to have high levels of autoantibodies to the protein.[5]
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.[8] Mutant mice deficient in Ku70 exhibit early aging.[9] 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.[10] (Also see
DNA damage theory of aging.)
Clinical
A mutation in this gene has been described in a set of 24 families with
autism.[11] 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
^Sjaarda CP, Wood S, McNaughton AJ, Taylor S, Hudson ML, Liu X, Guerin A, Ayub M (December 2019). "Exome sequencing identifies de novo splicing variant in XRCC6 in sporadic case of autism". Journal of Human Genetics. 65 (3): 287–296.
doi:
10.1038/s10038-019-0707-0.
PMID31827253.
S2CID209312195.
^Goedecke W, Eijpe M, Offenberg HH, van Aalderen M, Heyting C (Oct 1999). "Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis". Nature Genetics. 23 (2): 194–8.
doi:
10.1038/13821.
PMID10508516.
S2CID13443404.
^Grandvaux N, Grizot S, Vignais PV, Dagher MC (Feb 1999). "The Ku70 autoantigen interacts with p40phox in B lymphocytes". Journal of Cell Science. 112 (4): 503–13.
doi:
10.1242/jcs.112.4.503.
PMID9914162.
Featherstone C, Jackson SP (May 1999). "Ku, a DNA repair protein with multiple cellular functions?". Mutation Research. 434 (1): 3–15.
doi:
10.1016/s0921-8777(99)00006-3.
PMID10377944.
In addition to its role in NHEJ, Ku is also required for
telomere length maintenance and subtelomeric gene silencing.[7]
Ku was originally identified when patients with
systemic lupus erythematosus were found to have high levels of autoantibodies to the protein.[5]
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.[8] Mutant mice deficient in Ku70 exhibit early aging.[9] 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.[10] (Also see
DNA damage theory of aging.)
Clinical
A mutation in this gene has been described in a set of 24 families with
autism.[11] 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
^Sjaarda CP, Wood S, McNaughton AJ, Taylor S, Hudson ML, Liu X, Guerin A, Ayub M (December 2019). "Exome sequencing identifies de novo splicing variant in XRCC6 in sporadic case of autism". Journal of Human Genetics. 65 (3): 287–296.
doi:
10.1038/s10038-019-0707-0.
PMID31827253.
S2CID209312195.
^Goedecke W, Eijpe M, Offenberg HH, van Aalderen M, Heyting C (Oct 1999). "Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis". Nature Genetics. 23 (2): 194–8.
doi:
10.1038/13821.
PMID10508516.
S2CID13443404.
^Grandvaux N, Grizot S, Vignais PV, Dagher MC (Feb 1999). "The Ku70 autoantigen interacts with p40phox in B lymphocytes". Journal of Cell Science. 112 (4): 503–13.
doi:
10.1242/jcs.112.4.503.
PMID9914162.
Featherstone C, Jackson SP (May 1999). "Ku, a DNA repair protein with multiple cellular functions?". Mutation Research. 434 (1): 3–15.
doi:
10.1016/s0921-8777(99)00006-3.
PMID10377944.