Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Ercc1. (This text reflects annotations as of Wednesday, January 23, 2013.) MGI curation of this mouse gene is considered complete, including annotations derived from the biomedical literature as of April 23, 2008. If you know of any additional information regarding this mouse gene please let us know. Please supply mouse gene symbol and a PubMed ID.

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] The product of this gene functions in the nucleotide excision repair pathway, and is required for the repair of DNA lesions such as those induced by UV light or formed by electrophilic compounds including cisplatin. The encoded protein forms a heterodimer with the XPF endonuclease (also known as ERCC4), and the heterodimeric endonuclease catalyzes the 5' incision in the process of excising the DNA lesion. The heterodimeric endonuclease is also involved in recombinational DNA repair and in the repair of inter-strand crosslinks. Mutations in this gene result in cerebrooculofacioskeletal syndrome, and polymorphisms that alter expression of this gene may play a role in carcinogenesis. Multiple transcript variants encoding different isoforms have been found for this gene. The last exon of this gene overlaps with the CD3e molecule, epsilon associated protein gene on the opposite strand. [provided by RefSeq, Oct 2009]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Ercc1
  • performs the following molecular functions:
    • TFIID-class transcription factor binding ^[5]
  • is located in the following cellular components:
    • transcription factor TFIID complex ^[5]
• The gene product of Ercc1 has been shown to bind to the gene products of Ercc4. ^[1] Researchers have inferred, based on physical interactions, that the gene product of Ercc1
  • performs the following molecular functions:
    • TBP-class protein binding ^[5]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Ercc1
  • participates in the following biological processes:
    • cell development ^[10]
    • cell proliferation ^[12]
    • chromosome organization ^[8]
    • DNA recombination ^[7]
    • DNA repair ^[4]
    • double-strand break repair ^{[8, 11]}
    • germ cell development ^[11]
    • isotype switching ^[13]
    • male gonad development ^[11]
    • multicellular organism growth ^{[5, 9]}
    • multicellular organismal aging ^[9]
    • negative regulation of apoptotic process ^{[5, 11]}
    • nucleotide-excision repair ^[6]
    • oogenesis ^[4]
    • post-embryonic hemopoiesis ^[12]
    • pyrimidine dimer repair by nucleotide-excision repair ^[15]
    • replicative cell aging ^{[14, 16]}
    • response to DNA damage stimulus ^{[3, 7, 12, 16]}
    • response to X-ray ^[3]
    • spermatogenesis ^[4]
    • syncytium formation ^[10]
    • UV protection ^{[2, 6, 15]}
• Researchers have inferred, based on genetic interactions, that the gene product of Ercc1
  • participates in the following biological processes:
    • multicellular organism growth based on interactions with Ercc6, Xpa ^[5]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Ercc1:
  • participates in the following biological processes:
    • DNA recombination
    • mitotic recombination
    • negative regulation of telomere maintenance
    • nucleotide-excision repair
    • nucleotide-excision repair, DNA incision, 3'-to lesion
    • nucleotide-excision repair, DNA incision, 5'-to lesion
    • response to oxidative stress
  • performs the following molecular functions:
    • damaged DNA binding
    • protein C-terminus binding
    • protein domain specific binding
    • single-stranded DNA binding
  • is located in the following cellular components:
    • cytoplasm
    • nuclear chromosome, telomeric region
    • nucleotide-excision repair complex
    • nucleus

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Summary text based on GO annotations supported by structural data

• Ercc1 encodes a protein or proteins that contain the following InterPro domains: DNA repair protein rad10, Helix-hairpin-helix DNA-binding motif, class 1, Helix-hairpin-helix motif, Restriction endonuclease type II--like, RuvA domain 2-like, indicating that the gene product:
  • performs the following molecular functions:
    • DNA binding
    • endonuclease activity

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Ercc1 indicates that it:
  • performs the following molecular functions:
    • DNA binding
    • endonuclease activity
    • hydrolase activity
    • nuclease activity

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References

1. Chen J et al. (2012) Cathepsin cleavage of sirtuin 1 in endothelial progenitor cells mediates stress-induced premature senescence. Am J Pathol, 180:973-83. (PubMed:22234173)
2. Doig J et al. (2006) Mice with skin-specific DNA repair gene (Ercc1) inactivation are hypersensitive to ultraviolet irradiation-induced skin cancer and show more rapid actinic progression. Oncogene, 25:6229-38. (PubMed:16682947)
3. Griffin C et al. (2005) The involvement of key DNA repair pathways in the formation of chromosome rearrangements in embryonic stem cells. DNA Repair (Amst), 4:1019-27. (PubMed:15979950)
4. Hsia KT et al. (2003) DNA repair gene Ercc1 is essential for normal spermatogenesis and oogenesis and for functional integrity of germ cell DNA in the mouse. Development, 130:369-78. (PubMed:12466203)
5. Kamileri I et al. (2012) Defective transcription initiation causes postnatal growth failure in a mouse model of nucleotide excision repair (NER) progeria. Proc Natl Acad Sci U S A, 109:2995-3000. (PubMed:22323595)
6. McWhir J et al. (1993) Mice with DNA repair gene (ERCC-1) deficiency have elevated levels of p53, liver nuclear abnormalities and die before weaning [see comments] Nat Genet, 5:217-24. (PubMed:8275084)
7. Niedernhofer LJ et al. (2001) The structure-specific endonuclease Ercc1-Xpf is required for targeted gene replacement in embryonic stem cells. EMBO J, 20:6540-9. (PubMed:11707424)
8. Niedernhofer LJ et al. (2004) The structure-specific endonuclease Ercc1-Xpf is required to resolve DNA interstrand cross-link-induced double-strand breaks. Mol Cell Biol, 24:5776-87. (PubMed:15199134)
9. Niedernhofer LJ et al. (2006) A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature, 444:1038-43. (PubMed:17183314)
10. Nunez F et al. (2000) Nucleotide excision repair gene (ERCC1) deficiency causes G(2) arrest in hepatocytes and a reduction in liver binucleation: the role of p53 and p21. FASEB J, 14:1073-82. (PubMed:10834928)
11. Paul C et al. (2007) Deletion of genes implicated in protecting the integrity of male germ cells has differential effects on the incidence of DNA breaks and germ cell loss. PLoS ONE, 2:e989. (PubMed:17912366)
12. Prasher JM et al. (2005) Reduced hematopoietic reserves in DNA interstrand crosslink repair-deficient Ercc1(-/-) mice. EMBO J, 24:861-71. (PubMed:15692571)
13. Schrader CE et al. (2004) Deletion of the nucleotide excision repair gene Ercc1 reduces immunoglobulin class switching and alters mutations near switch recombination junctions. J Exp Med, 200:321-30. (PubMed:15280420)
14. van de Ven M et al. (2006) Adaptive Stress Response in Segmental Progeria Resembles Long-Lived Dwarfism and Calorie Restriction in Mice. PLoS Genet, 2:e192. (PubMed:17173483)
15. Van Sloun PP et al. (1999) The role of nucleotide excision repair in protecting embryonic stem cells from genotoxic effects of UV-induced DNA damage. Nucleic Acids Res, 27:3276-82. (PubMed:10454634)
16. Weeda G et al. (1997) Disruption of mouse ERCC1 results in a novel repair syndrome with growth failure, nuclear abnormalities and senescence. Curr Biol, 7:427-39. (PubMed:9197240)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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