ABSTRACT
I provide a personal account of the discovery, cloning and functional analyses of the human XPG gene. Mutations in this gene can give rise to the group G form of xeroderma pigmentosum (XP) and, in some cases, to severe early onset Cockayne syndrome (CS). The XPG protein has well established catalytic and structural roles in nucleotide excision repair (NER) and it acts as a cofactor for a DNA glycosylase that removes oxidised pyrimidines from DNA. XPG may also be involved in transcription-coupled repair of this kind of damage, in transcription by RNA polymerase II, and perhaps in other processes too. Our current knowledge of this important protein is largely based on some excellent, highly focussed science. But good luck, serendipity and scientific scandal have also made major contributions to this unfinished story.
Subject(s)
DNA-Binding Proteins , Animals , Cockayne Syndrome/history , Cockayne Syndrome/metabolism , DNA Repair , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/genetics , DNA-Binding Proteins/history , DNA-Binding Proteins/metabolism , Deoxyribonuclease (Pyrimidine Dimer)/metabolism , Endonucleases/chemistry , Endonucleases/genetics , Endonucleases/history , Endonucleases/metabolism , History, 19th Century , History, 20th Century , Humans , Nuclear Proteins , Transcription FactorsABSTRACT
The "Dutch DNA Repair Group" was established about 35 years ago. In this brief historical review some of the crucial decisions are described that have contributed to the relative success of the research of this group. The emphasis of the work of this group has been for many years on the genetic analysis of nucleotide excision repair (NER) and genetic diseases based on defects in this repair process: xeroderma pigmentosum (XP), Cockayne syndrome and trichothiodystrophy.
