Xeroderma Pigmentosum Group F Caused by a Defect in a Structure-Specific DNA Repair Endonuclease

Cell. 1996 Sep 6;86(5):811-22. doi: 10.1016/s0092-8674(00)80155-5.

Abstract

Nucleotide excision repair, which is defective in xeroderma pigmentosum (XP), involves incision of a DNA strand on each side of a lesion. We isolated a human gene homologous to yeast Rad1 and found that it corrects the repair defects of XP group F as well as rodent groups 4 and 11. Causative mutations and strongly reduced levels of encoded protein were identified in XP-F patients. The XPF protein was purified from mammalian cells in a tight complex with ERCC1. This complex is a structure-specific endonuclease responsible for the 5' incision during repair. These results demonstrate that the XPF, ERCC4, and ERCC11 genes are equivalent, complete the isolation of the XP genes that form the core nucleotide excision repair system, and solve the catalytic function of the XPF-containing complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cloning, Molecular
  • DNA / chemistry
  • DNA / metabolism
  • DNA Mutational Analysis
  • DNA Repair / genetics*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / isolation & purification
  • DNA-Binding Proteins / metabolism
  • Endonucleases / chemistry
  • Endonucleases / genetics*
  • Endonucleases / isolation & purification
  • Endonucleases / metabolism
  • Fibroblasts
  • Fungal Proteins / genetics
  • Genetic Complementation Test
  • Humans
  • Molecular Sequence Data
  • Molecular Weight
  • Multienzyme Complexes
  • Nucleic Acid Conformation
  • Protein Binding
  • Proteins / chemistry
  • Proteins / isolation & purification
  • Proteins / metabolism
  • Radiation Tolerance
  • Rodentia
  • Sequence Homology, Amino Acid
  • Xeroderma Pigmentosum / enzymology*
  • Xeroderma Pigmentosum / genetics*

Substances

  • DNA-Binding Proteins
  • Fungal Proteins
  • Multienzyme Complexes
  • Proteins
  • xeroderma pigmentosum group F protein
  • DNA
  • ERCC1 protein, human
  • Endonucleases

Associated data

  • GENBANK/U64315