Nucleotide excision repair subpathways

While defects in protein XPD often cause typical XP symptoms, some defects in the same protein lead to trichothiodystrophy (TTD, brittle hair disease). The hair is sulfur deficient, and scaly skin (ichthyosis, Box 8-F), mental retardation, and other symptoms are observed.0 Like their yeast counterparts (proteins RAD3 and RAD25), XPB and XPD are both DNA helicases.0 They also constitute distinct subunits of the human transcription factor TFIIHP, which is discussed in Chapter 28. It seems likely that XPD is involved in transcription-coupled repair (TCR) of DNA.° °i-s This is a subpathway of the nucleotide excision repair (NER) pathway, which allows for rapid repair of the transcribed strand of DNA. This is important in tissues such as skin, where the global NER process may be too slow to keep up with the need for rapid protein synthesis. Transcription-coupled repair also appears to depend upon proteins CSA and CSB, defects which may result in the rare cockayne syndrome.13 0 4 11 Patients are not only photosensitive but have severe mental and physical retardation including skeletal defects and a wizened appearance. 

Available evidence indicates that PCNA is also involved in DNA nucleotide excision-repair. This role is exemplified by the demonstration that PCNA can be found associated with chromatin at all phases of the cell cycle after ultraviolet irradiation in vitro (Toschi and Bravo, 1988). Recently it was shown that not only DNA polymerase delta but DNA polymerases beta and epsilon are also involved in the base excision repair subpathways (Dianov et al., 1999). In addition, PCNA may be expressed by noncycling cells in vivo which are undergoing DNA repair (Hall et al., 1993). 

Hanawalt PC (2002) Subpathways of nucleotide excision repair and their regulation. Oncogene 21 8949-8956. 

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