[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.
[ERCC1_HUMAN] Structure-specific DNA repair endonuclease responsible for the 5'-incision during DNA repair.
Human ERCC1/XPF is a structure-specific endonuclease involved in multiple DNA repair pathways. We present the solution structure of the non-catalytic ERCC1 central domain. Although this domain shows structural homology with the catalytically active XPF nuclease domain, functional investigation reveals a completely distinct function for the ERCC1 central domain by performing interactions with both XPA and single-stranded DNA. These interactions are non-competitive and can occur simultaneously through distinct interaction surfaces. Interestingly, the XPA binding by ERCC1 and the catalytic function of XPF are dependent on a structurally homologous region of the two proteins. Although these regions are strictly conserved in each protein family, amino acid composition and surface characteristics are distinct. We discuss the possibility that after XPF gene duplication, the redundant ERCC1 central domain acquired novel functions, thereby increasing the fidelity of eukaryotic DNA repair.
Analysis of the XPA and ssDNA-binding surfaces on the central domain of human ERCC1 reveals evidence for subfunctionalization.,Tripsianes K, Folkers GE, Zheng C, Das D, Grinstead JS, Kaptein R, Boelens R Nucleic Acids Res. 2007;35(17):5789-98. Epub 2007 Aug 24. PMID:17720715
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↑ 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
↑ Tripsianes K, Folkers GE, Zheng C, Das D, Grinstead JS, Kaptein R, Boelens R. Analysis of the XPA and ssDNA-binding surfaces on the central domain of human ERCC1 reveals evidence for subfunctionalization. Nucleic Acids Res. 2007;35(17):5789-98. Epub 2007 Aug 24. PMID:17720715 doi:10.1093/nar/gkm503