XRCC4:LIG4, NHEJ1 and POLL or POLM bind DNA DSBs in NHEJ

Stable Identifier
R-HSA-5693574
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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A complex consisting of XRCC4 homodimer and DNA ligase IV (LIG4) (Sibanda et al. 2001) is recruited to the synaptic complex consisting of PRKDC (DNA-PKcs), XRCC5, XRCC6, DCLRE1C (ARTEMIS) and ligatable DNA double strand break (DSB) ends (Critchlow and Jackson 1997, Leber et al. 1998, Malu et al. 2012). XRCC4 directly interacts with XRCC5:XRCC6 (McElhinny et al. 2000, Hsu et al. 2002), while LIG4 directly interacts with PRKDC (Hsu et al. 2002) and DCLRE1C (Malu et al. 2012). NHEJ1 (XLF) homodimer binds XRCC4 and is recruited to DNA DSBs together with XRCC4 and LIG4, where it acts as a facilitator of LIG4 activity (Ahnesorg et al. 2006, Buck et al. 2006, Tsai et al. 2007, Li et al. 2008). DNA polymerases mu (POLM) or lambda (POLL) are recruited to DNA DSBs through interaction with the Ku complex (XRCC5:XRCC6) and XRCC4 (Mahajan et al. 2002, Lee et al. 2004, Fan and Wu 2004).

Literature References
PubMed ID Title Journal Year
17470781 Cernunnos/XLF promotes the ligation of mismatched and noncohesive DNA ends

Tsai, CJ, Kim, SA, Chu, G

Proc. Natl. Acad. Sci. U.S.A. 2007
16439205 XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining

Ahnesorg, P, Smith, P, Jackson, SP

Cell 2006
12509254 Defining interactions between DNA-PK and ligase IV/XRCC4

Hsu, HL, Yannone, SM, Chen, DJ

DNA Repair (Amst.) 2002
11702069 Crystal structure of an Xrcc4-DNA ligase IV complex

Sibanda, BL, Critchlow, SE, Begun, J, Pei, XY, Jackson, SP, Blundell, TL, Pellegrini, L

Nat. Struct. Biol. 2001
16439204 Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly

Buck, D, Malivert, L, de Chasseval, R, Barraud, A, Fondan├Ęche, MC, Sanal, O, Plebani, A, St├ęphan, JL, Hufnagel, M, Le Deist, F, Fischer, A, Durandy, A, de Villartay, JP, Revy, P

Cell 2006
18046455 Crystal structure of human XLF/Cernunnos reveals unexpected differences from XRCC4 with implications for NHEJ

Li, Y, Chirgadze, DY, Bolanos-Garcia, VM, Sibanda, BL, Davies, OR, Ahnesorg, P, Jackson, SP, Blundell, TL

EMBO J. 2008
22529269 Artemis C-terminal region facilitates V(D)J recombination through its interactions with DNA Ligase IV and DNA-PKcs

Malu, S, De Ioannes, P, Kozlov, M, Greene, M, Francis, D, Hanna, M, Pena, J, Escalante, CR, Kurosawa, A, Erdjument-Bromage, H, Tempst, P, Adachi, N, Vezzoni, P, Villa, A, Aggarwal, AK, Cortes, P

J. Exp. Med. 2012
12077346 Association of DNA polymerase mu (pol mu) with Ku and ligase IV: role for pol mu in end-joining double-strand break repair

Mahajan, KN, Nick McElhinny, SA, Mitchell, BS, Ramsden, DA

Mol. Cell. Biol. 2002
15451442 DNA polymerase lambda can elongate on DNA substrates mimicking non-homologous end joining and interact with XRCC4-ligase IV complex

Fan, W, Wu, X

Biochem. Biophys. Res. Commun. 2004
9430729 The XRCC4 gene product is a target for and interacts with the DNA-dependent protein kinase.

Leber, R, Wise, TW, Mizuta, R, Meek, K

J Biol Chem 1998
14561766 Implication of DNA polymerase lambda in alignment-based gap filling for nonhomologous DNA end joining in human nuclear extracts

Lee, JW, Blanco, L, Zhou, T, Garcia-Diaz, M, Bebenek, K, Kunkel, TA, Wang, Z, Povirk, LF

J. Biol. Chem. 2004
10757784 Ku recruits the XRCC4-ligase IV complex to DNA ends

Nick McElhinny, SA, Snowden, CM, McCarville, J, Ramsden, DA

Mol. Cell. Biol. 2000
9259561 Mammalian DNA double-strand break repair protein XRCC4 interacts with DNA ligase IV.

Critchlow, SE, Bowater, RP

Curr Biol 1997
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