LIG4

Ligaza IV, DNK, ATP-zavisna
Ligaza IV, DNK, ATP-zavisna
	PDB prikaz baziran na 1ik9.
Dostupne strukture
	1IK9, 2E2W, 3II6
Identifikatori
Simbol	LIG4
Vanjski ID	OMIM: 601837 MGI: 1335098 HomoloGene: 1736 GeneCards: LIG4 Gene
EC broj	6.5.1.1
Ontologija gena
Molekularna funkcija	• vezivanje nukleotida; • DNK vezivanje; • aktivnost DNK ligaze; • aktivnost DNK ligaze (ATP); • proteinsko vezivanje; • ATP vezivanje; • vezivanje protein C-terminusa; • aktivnost ligaze; • vezivanje metalnog jona;
Celularna komponenta	• kondenzovani hromozom; • intracelularni; • jedro; • nukleoplazma; • nukleolus; • citoplazma; • ćelijska membrana; • fokalna adhezija; • DNK zavisna proteinska kinaza - DNK ligaza 4 kompleks; • kompleks DNK ligaze IV; • kompleks nehomolognog spajanja krajeva;
Biološki proces	• popravka jednolančanih prekida; • in utero embrionski razvoj; • pro-B ćelijska diferencijacija; • replikacija DNK; • ligacija DNK; • popravka DNK; • popravka dvolančanih prekida;
Pregled RNK izražavanja
	podaci
Ortolozi
Vrsta	Čovek
Entrez	3981
Ensembl	ENSG00000174405
UniProt	P49917
RefSeq (mRNA)	NM_001098268.1
RefSeq (protein)	NP_001091738.1
Lokacija (UCSC)	Chr 13:; 108.86 - 108.87 Mb
PubMed pretraga	[1]

LIG4 je gen koji kodira proteinsku DNK ligazu IV.^[1] Ovaj protein je ATP zavisna DNK ligaza koja spaja dvolančane prekide tokom nehomolognog spajanja krajeva u putu popravke prekida dvostrukog lanca. On je takođe esencijalan za V(D)J rekombinaciju.

Defekti ovog gena uzrokuju LIG4 sindrom. Lig4 homolog u kvascu je Dnl4.

Interakcije uredi

Lig4 formira kompleks sa XRCC4,^[2]^[3] i dalje interaguje sa DNK zavisnom proteinskom kinazom (DNA-PK) i XLF/Cernunnos.

Reference uredi

^ „Entrez Gene: LIG4 ligase IV, DNA, ATP-dependent”.
^ Deshpande Rajashree A; Wilson Thomas E (2007). „Modes of interaction among yeast Nej1, Lif1 and Dnl4 proteins and comparison to human XLF, XRCC4 and Lig4”. DNA Repair (Amst.). Netherlands. 6 (10): 1507—16. ISSN 1568-7864. PMC 2064958  . PMID 17567543. doi:10.1016/j.dnarep.2007.04.014.
^ Sibanda BL, Critchlow SE, Begun J, Pei XY, Jackson SP, Blundell TL, Pellegrini L (2001). „Crystal structure of an Xrcc4-DNA ligase IV complex”. Nat. Struct. Biol. United States. 8 (12): 1015—9. ISSN 1072-8368. PMID 11702069. doi:10.1038/nsb725.

Literatura uredi

Wei YF; Robins P; Carter K; et al. (1995). „Molecular cloning and expression of human cDNAs encoding a novel DNA ligase IV and DNA ligase III, an enzyme active in DNA repair and recombination”. Mol. Cell. Biol. 15 (6): 3206—16. PMC 230553  . PMID 7760816.
Robins P, Lindahl T (1996). „DNA ligase IV from HeLa cell nuclei”. J. Biol. Chem. 271 (39): 24257—61. PMID 8798671. doi:10.1074/jbc.271.39.24257.
Grawunder U; Wilm M; Wu X; et al. (1997). „Activity of DNA ligase IV stimulated by complex formation with XRCC4 protein in mammalian cells”. Nature. 388 (6641): 492—5. PMID 9242410. doi:10.1038/41358.
Critchlow SE, Bowater RP, Jackson SP (1997). „Mammalian DNA double-strand break repair protein XRCC4 interacts with DNA ligase IV”. Curr. Biol. 7 (8): 588—98. PMID 9259561. doi:10.1016/S0960-9822(06)00258-2.
Grawunder U, Zimmer D, Leiber MR (1998). „DNA ligase IV binds to XRCC4 via a motif located between rather than within its BRCT domains”. Curr. Biol. 8 (15): 873—6. PMID 9705934. doi:10.1016/S0960-9822(07)00349-1.
Grawunder U; Zimmer D; Fugmann S; et al. (1998). „DNA ligase IV is essential for V(D)J recombination and DNA double-strand break repair in human precursor lymphocytes”. Mol. Cell. 2 (4): 477—84. PMID 9809069. doi:10.1016/S1097-2765(00)80147-1.
Riballo E; Critchlow SE; Teo SH; et al. (1999). „Identification of a defect in DNA ligase IV in a radiosensitive leukaemia patient”. Curr. Biol. 9 (13): 699—702. PMID 10395545. doi:10.1016/S0960-9822(99)80311-X.
Kim ST, Lim DS, Canman CE, Kastan MB (2000). „Substrate specificities and identification of putative substrates of ATM kinase family members”. J. Biol. Chem. 274 (53): 37538—43. PMID 10608806. doi:10.1074/jbc.274.53.37538.
Nick McElhinny SA, Snowden CM, McCarville J, Ramsden DA (2000). „Ku Recruits the XRCC4-Ligase IV Complex to DNA Ends”. Mol. Cell. Biol. 20 (9): 2996—3003. PMC 85565  . PMID 10757784. doi:10.1128/MCB.20.9.2996-3003.2000.
Chen L, Trujillo K, Sung P, Tomkinson AE (2000). „Interactions of the DNA ligase IV-XRCC4 complex with DNA ends and the DNA-dependent protein kinase”. J. Biol. Chem. 275 (34): 26196—205. PMID 10854421. doi:10.1074/jbc.M000491200.
Lee KJ, Huang J, Takeda Y, Dynan WS (2000). „DNA ligase IV and XRCC4 form a stable mixed tetramer that functions synergistically with other repair factors in a cell-free end-joining system”. J. Biol. Chem. 275 (44): 34787—96. PMID 10945980. doi:10.1074/jbc.M004011200.
Riballo E; Doherty AJ; Dai Y; et al. (2001). „Cellular and biochemical impact of a mutation in DNA ligase IV conferring clinical radiosensitivity”. J. Biol. Chem. 276 (33): 31124—32. PMID 11349135. doi:10.1074/jbc.M103866200.
Sibanda BL; Critchlow SE; Begun J; et al. (2002). „Crystal structure of an Xrcc4-DNA ligase IV complex”. Nat. Struct. Biol. 8 (12): 1015—9. PMID 11702069. doi:10.1038/nsb725.
O'Driscoll M; Cerosaletti KM; Girard PM; et al. (2002). „DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency”. Mol. Cell. 8 (6): 1175—85. PMID 11779494. doi:10.1016/S1097-2765(01)00408-7.
Kuschel B; Auranen A; McBride S; et al. (2002). „Variants in DNA double-strand break repair genes and breast cancer susceptibility”. Hum. Mol. Genet. 11 (12): 1399—407. PMID 12023982. doi:10.1093/hmg/11.12.1399.
Mahajan KN, Nick McElhinny SA, Mitchell BS, Ramsden DA (2002). „Association of DNA Polymerase μ (pol μ) with Ku and Ligase IV: Role for pol μ in End-Joining Double-Strand Break Repair”. Mol. Cell. Biol. 22 (14): 5194—202. PMC 139779  . PMID 12077346. doi:10.1128/MCB.22.14.5194-5202.2002.
Roth DB (2002). „Amplifying mechanisms of lymphomagenesis”. Mol. Cell. 10 (1): 1—2. PMID 12150897. doi:10.1016/S1097-2765(02)00573-7.
Smogorzewska A; Karlseder J; Holtgreve-Grez H; et al. (2003). „DNA ligase IV-dependent NHEJ of deprotected mammalian telomeres in G1 and G2”. Curr. Biol. 12 (19): 1635—44. PMID 12361565. doi:10.1016/S0960-9822(02)01179-X.
Roddam PL; Rollinson S; O'Driscoll M; et al. (2003). „Genetic variants of NHEJ DNA ligase IV can affect the risk of developing multiple myeloma, a tumour characterised by aberrant class switch recombination”. J. Med. Genet. 39 (12): 900—5. PMC 1757220  . PMID 12471202. doi:10.1136/jmg.39.12.900.
Strausberg RL; Feingold EA; Grouse LH; et al. (2003). „Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences”. Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899—903. PMC 139241  . PMID 12477932. doi:10.1073/pnas.242603899.
Nicholas C. Price; Lewis Stevens (1999). Fundamentals of Enzymology: The Cell and Molecular Biology of Catalytic Proteins (Third изд.). USA: Oxford University Press. ISBN 019850229X.
Eric J. Toone (2006). Advances in Enzymology and Related Areas of Molecular Biology, Protein Evolution (Volume 75 изд.). Wiley-Interscience. ISBN 0471205036.
Branden C; Tooze J. Introduction to Protein Structure. New York, NY: Garland Publishing. ISBN 0-8153-2305-0.
Irwin H. Segel. Enzyme Kinetics: Behavior and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems (Book 44 изд.). Wiley Classics Library. ISBN 0471303097.

Vidi još uredi

DNK ligaza

Spoljašnje veze uredi

[entrez-1] „Entrez Gene: LIG4 ligase IV, DNA, ATP-dependent”.

[pmid17567543-2] Deshpande Rajashree A; Wilson Thomas E (2007). „Modes of interaction among yeast Nej1, Lif1 and Dnl4 proteins and comparison to human XLF, XRCC4 and Lig4”. DNA Repair (Amst.). Netherlands. 6 (10): 1507—16. ISSN 1568-7864. PMC 2064958  . PMID 17567543. doi:10.1016/j.dnarep.2007.04.014.

[pmid11702069-3] Sibanda BL, Critchlow SE, Begun J, Pei XY, Jackson SP, Blundell TL, Pellegrini L (2001). „Crystal structure of an Xrcc4-DNA ligase IV complex”. Nat. Struct. Biol. United States. 8 (12): 1015—9. ISSN 1072-8368. PMID 11702069. doi:10.1038/nsb725.

[1]

[2]

[3]