XRCC4:LIG4 ligates DNA DSB ends during NHEJ

Stable Identifier
Reaction [transition]
Homo sapiens
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The DNA ligase complex composed of DNA ligase 4 (LIG4) and the XRCC4 homodimer (Sibanda et al. 2000) catalyzes ligation of DNA double strand break (DSB) ends during non-homologous end joining (NHEJ). The XRCC4:LIG4 complex is recruited to NHEJ sites through interaction of its subunits with XRCC5:XRCC6 (Ku complex), PRKDC (DNA-PKcs) and DCLRE1C (ARTEMIS) (McElhinny et al. 2000, Hsu et al. 2002, Malu et al. 2012). Phosphorylation of XRCC4 by PRKDC may regulate the activity of the ligase complex (Lee et al. 2004). XRCC4:LIG4 can ligate incompatible DNA DSB ends, and may also ligate across single nucleotide gaps (Gu et al. 2007). The presence of the accessory protein NHEJ1 (XLF) facilitates XRCC4:LIG4 ligase activity, especially at mismatched DNA DSB ends (Ahnesorg et al. 2006, Buck et al. 2006, Tsai et al. 2007). Depending on other types of DNA damage present at DNA DSBs, NHEJ can result in error-free products, produce dsDNA with microdeletions and/or mismatched bases, or result in translocations (reviewed by Povirk 2012).
Literature References
PubMed ID Title Journal Year
24236237 Processing of damaged DNA ends for double-strand break repair in mammalian cells

Povirk, LF

ISRN Mol Biol 2012
16439205 XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining

Smith, P, Jackson, SP, Ahnesorg, P

Cell 2006
17470781 Cernunnos/XLF promotes the ligation of mismatched and noncohesive DNA ends

Kim, SA, Chu, G, Tsai, CJ

Proc. Natl. Acad. Sci. U.S.A. 2007
22529269 Artemis C-terminal region facilitates V(D)J recombination through its interactions with DNA Ligase IV and DNA-PKcs

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

J. Exp. Med. 2012
12509254 Defining interactions between DNA-PK and ligase IV/XRCC4

Chen, DJ, Yannone, SM, Hsu, HL

DNA Repair (Amst.) 2002
17290226 XRCC4:DNA ligase IV can ligate incompatible DNA ends and can ligate across gaps

Lieber, MR, Lu, H, Goodman, MF, Shimazaki, N, Tippin, B, Gu, J

EMBO J. 2007
11702069 Crystal structure of an Xrcc4-DNA ligase IV complex

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

Nat. Struct. Biol. 2001
9826654 DNA end-joining catalyzed by human cell-free extracts.

West, SC, Baumann, P

Proc Natl Acad Sci U S A 1998
10757784 Ku recruits the XRCC4-ligase IV complex to DNA ends

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

Mol. Cell. Biol. 2000
16439204 Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly

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

Cell 2006
15177042 Identification of DNA-PKcs phosphorylation sites in XRCC4 and effects of mutations at these sites on DNA end joining in a cell-free system

Udayakumar, D, Jovanovic, M, Dynan, WS, Bladen, CL, Lee, KJ

DNA Repair (Amst.) 2004
Catalyst Activity

DNA ligase activity of p-T2609,S2612,T2638,T2647-PRKDC:XRCC5:XRCC6:p-S516,S645-DCLRE1C:XRCC4:LIG4:NHEJ1:POLL,POLM:Extended ligatable DNA DSB ends [nucleoplasm]

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