| Structural highlights
1z00 is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[ERCC1_HUMAN] Defects in ERCC1 are the cause of cerebro-oculo-facio-skeletal syndrome type 4 (COFS4) [MIM:610758]. COFS is a degenerative autosomal recessive disorder of prenatal onset affecting the brain, eye and spinal cord. After birth, it leads to brain atrophy, hypoplasia of the corpus callosum, hypotonia, cataracts, microcornea, optic atrophy, progressive joint contractures and growth failure. Facial dysmorphism is a constant feature. Abnormalities of the skull, eyes, limbs, heart and kidney also occur.[1] [ERCC4_HUMAN] Defects in ERCC4 are the cause of xeroderma pigmentosum complementation group F (XP-F) [MIM:278760]; also known as xeroderma pigmentosum VI (XP6). XP-F is an autosomal recessive disease characterized by hypersensitivity of the skin to sunlight followed by high incidence of skin cancer and frequent neurologic abnormalities.[2] [3] [4] Defects in ERCC4 are a cause of XFE progeroid syndrome (XFEPS) [MIM:610965]. This syndrome is illustrated by one patient who presented with dwarfism, cachexia and microcephaly.[5]
Function
[ERCC1_HUMAN] Structure-specific DNA repair endonuclease responsible for the 5'-incision during DNA repair. [ERCC4_HUMAN] Structure-specific DNA repair endonuclease responsible for the 5-prime incision during DNA repair. Involved in homologous recombination that assists in removing interstrand cross-link.[6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The human ERCC1/XPF complex is a structure-specific endonuclease with defined polarity that participates in multiple DNA repair pathways. We report the heterodimeric structure of the C-terminal domains of both proteins responsible for ERCC1/XPF complex formation. Both domains exhibit the double helix-hairpin-helix motif (HhH)2, and they are related by a pseudo-2-fold symmetry axis. In the XPF domain, the hairpin of the second motif is replaced by a short turn. The ERCC1 domain folds properly only in the presence of the XPF domain, which implies a role for XPF as a scaffold for the folding of ERCC1. The intersubunit interactions are largely hydrophobic in nature. NMR titration data show that only the ERCC1 domain of the ERCC1/XPF complex is involved in DNA binding. On the basis of these findings, we propose a model for the targeting of XPF nuclease via ERCC1-mediated interactions in the context of nucleotide excision repair.
The structure of the human ERCC1/XPF interaction domains reveals a complementary role for the two proteins in nucleotide excision repair.,Tripsianes K, Folkers G, Ab E, Das D, Odijk H, Jaspers NG, Hoeijmakers JH, Kaptein R, Boelens R Structure. 2005 Dec;13(12):1849-58. PMID:16338413[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jaspers NG, Raams A, Silengo MC, Wijgers N, Niedernhofer LJ, Robinson AR, Giglia-Mari G, Hoogstraten D, Kleijer WJ, Hoeijmakers JH, Vermeulen W. First reported patient with human ERCC1 deficiency has cerebro-oculo-facio-skeletal syndrome with a mild defect in nucleotide excision repair and severe developmental failure. Am J Hum Genet. 2007 Mar;80(3):457-66. Epub 2007 Jan 29. PMID:17273966 doi:S0002-9297(07)60094-9
- ↑ Sijbers AM, de Laat WL, Ariza RR, Biggerstaff M, Wei YF, Moggs JG, Carter KC, Shell BK, Evans E, de Jong MC, Rademakers S, de Rooij J, Jaspers NG, Hoeijmakers JH, Wood RD. Xeroderma pigmentosum group F caused by a defect in a structure-specific DNA repair endonuclease. Cell. 1996 Sep 6;86(5):811-22. PMID:8797827
- ↑ Matsumura Y, Nishigori C, Yagi T, Imamura S, Takebe H. Characterization of molecular defects in xeroderma pigmentosum group F in relation to its clinically mild symptoms. Hum Mol Genet. 1998 Jun;7(6):969-74. PMID:9580660
- ↑ Sijbers AM, van Voorst Vader PC, Snoek JW, Raams A, Jaspers NG, Kleijer WJ. Homozygous R788W point mutation in the XPF gene of a patient with xeroderma pigmentosum and late-onset neurologic disease. J Invest Dermatol. 1998 May;110(5):832-6. PMID:9579555 doi:10.1046/j.1523-1747.1998.00171.x
- ↑ Niedernhofer LJ, Garinis GA, Raams A, Lalai AS, Robinson AR, Appeldoorn E, Odijk H, Oostendorp R, Ahmad A, van Leeuwen W, Theil AF, Vermeulen W, van der Horst GT, Meinecke P, Kleijer WJ, Vijg J, Jaspers NG, Hoeijmakers JH. A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature. 2006 Dec 21;444(7122):1038-43. PMID:17183314 doi:nature05456
- ↑ Svendsen JM, Smogorzewska A, Sowa ME, O'Connell BC, Gygi SP, Elledge SJ, Harper JW. Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair. Cell. 2009 Jul 10;138(1):63-77. PMID:19596235 doi:S0092-8674(09)00777-6
- ↑ Tripsianes K, Folkers G, Ab E, Das D, Odijk H, Jaspers NG, Hoeijmakers JH, Kaptein R, Boelens R. The structure of the human ERCC1/XPF interaction domains reveals a complementary role for the two proteins in nucleotide excision repair. Structure. 2005 Dec;13(12):1849-58. PMID:16338413 doi:10.1016/j.str.2005.08.014
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