Linked Life Data

48887Pathway591

Source:http://www.reactome.org/biopax/48887Pathway591

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Authored: Lees-Miller, S, 2003-07-14 15:03:25, Edited: Joshi-Tope, G, 0000-00-00 00:00:00, Reviewed: West, SC, 0000-00-00 00:00:00, The NHEJ pathway is initiated in response to the formation of a DNA double-strand break (DSB) induced by a DNA-damaging agent such as ionizing radiation. First, the Ku70/80 heterodimer binds to the ends of the DSB. The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) is then recruited to DNA-bound Ku to form the DNA-PK holoenzyme. The ends of the break are brought together as two molecules of DNA-PK (one at each end of the break) are joined in a synaptic complex. Other factors, such as polynucleotide kinase (PNK), Artemis, the MRE complex, hTdp1 or the Werner Syndrome protein (WRN) may be required for processing of the DNA ends prior to end rejoining, but exactly when processing takes place is not known. Following the formation of the synaptic complex, the XRCC4/DNA ligase IV complex is recruited. Prior to end rejoining, protein factors must be removed from the DNA. This may involve DNA-PK autophosphorylation (Chan and Lees-Miller, 1996; Douglas et al., 2001; 2002; Merkle et al., 2002). After removal of the repair factors, the DNA ends are ligated and the DNA is repaired. Both Mg-ATP and the protein kinase activity of DNA-PKcs are required for NHEJ (Kurimasa et al.,1999; Kienker et al, 2000; Baumann and West, 1998), probably through phosphorylation of DNA-PKcs and/or other proteins. In addition, inositol hexaphosphate (IP6) stimulates end joining in vitro (Hanakahi et al., 2000) and binds to Ku, but its precise role in NHEJ is unknown.
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Nonhomologous End-joining (NHEJ)
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