Association of Ku heterodimer with ends of DNA double-strand break

Stable Identifier
R-HSA-5693599
Type
Reaction [dissociation]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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Ionizing radiation (IR) induces single-strand breaks, i.e., cleavage of the phosphodiester backbone. When two single-strand breaks occur within approximately 10 base pairs, a DNA double-strand break (DSB) results. IR-induced DSBs are complex DNA damage lesions, frequently containing base damage, 5'-OH groups, and 3'-hydroxy or phosphoglycolate groups that must be removed prior to ligation in the final step of NHEJ (Friedberg et al, 1995; Nikjoo et al, 2001; Valerie and Povirk, 2003). The Ku70/80 heterodimer (XRCC5:XRCC6) (Walker et al., 2001) binds to the ends of the double-strand break. Ku can translocate inwards from the site of the break in an ATP-independent manner (reviewed in Dynan and Yoo, 1998). Binding of XRCC5:XRCC6 to DNA DSBs competes away the MRN complex and associated proteins from the DNA DSB (Sun et al. 2012).
Literature References
PubMed ID Title Journal Year
12947387 Regulation and mechanisms of mammalian double-strand break repair.

Valerie, K, Povirk, LF

Oncogene 2003
22179609 Human Ku70/80 protein blocks exonuclease 1-mediated DNA resection in the presence of human Mre11 or Mre11/Rad50 protein complex

Sun, J, Chen, DJ, Davis, AJ, Lee, KJ

J. Biol. Chem. 2012
11604075 Computational approach for determining the spectrum of DNA damage induced by ionizing radiation.

Goodhead, DT, O'Neill, P, Wilson, WE, Nikjoo, H

Radiat Res 2001
  DNA Repair and Mutagenesis

Friedberg, EC, Siede, W, Walker, GC

  1995
9512523 Interaction of Ku protein and DNA-dependent protein kinase catalytic subunit with nucleic acids.

Dynan, WS, Yoo, S

Nucleic Acids Res 1998
11493912 Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair.

Goldberg, J, Corpina, RA, Walker, JR

Nature 2001
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