Nucleotide excision repair transcription coupled

Rad26 Rad26p S. cerevisiae Deflp, Associates with RNA pol II Transcription coupled nucleotide excision repair [319,320]. 

CSB/ERCC6 CSB Human Associates with a subset of Pol II complexes Mutation causes Cockayne syndrome, a defect in transcription coupled nucleotide excision repair [321,322]. Human Rad26p homolog... 

Furuta T, Ueda T, Aune G et al. Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cells. Cancer Res 2002,62 4899 902. 

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. 

Keywords Direct repair Base excision repair (BER) Nucleotide excision repair (NER) Transcription-coupled repair HR NHEJ DNA repair polymorphisms ... 

Fousteri, M., and Mullenders, L. H. (2008). Transcription-coupled nucleotide excision repair in mammalian cells Molecular mechanisms and biological effects. Cell Res 18, 73-84. 

TFIIH also partidpates in another important cellular function, namely nucleotide excision repair of damaged DNA. This function accounts for the observation that transcription and the removal of bulky base adducts by nucleotide excision repair (NER) are coupled. An increased repair of DNA damage by NER is observed while a gene is being transcribed. During transcription-coupled repair, TFIIH assembles with other repair proteins into a large repair complex, allowing for the removal of DNA adducts. 

In the present chapter, we have explained the beneficial role of trabectedin treatment against ovarian cancer s and we have shown its manageable adverse effects. We have concluded that compared to the significant risks of recurrence and resistance of ovarian cancer to the available therapeutic strategies, trabectedin can be used as an alternative therapeutic method. Moreover, there are numerous clinical studies on the efficacy and side effects of trabectedin and, therefore, we can easily take a decision about its most effective doses needed for obtaining anticancer effects. To conclude, it seems that transcription -coupled nucleotide excision repair mechanism plays a pivotal role in the anticancer effects of trabectedin. 

Fig. 2. The two main pathways of nucleotide excision repair (NER), global genome repair (GG-NER) and transcription-coupled repair (TC-NER) (A) and the common NER pathway. The NER mechanism consists of the removal of a short stretch of DNA containing the lesion and the subsequent restoration of this lesion using the non-damaged DNA strand as a template. GG-NER removes lesions in non-transcribed domains of the genome or non-transcribed strands in the transcribed domains TC-NER removes lesions from the transcribed strand of active genes (modified from Fousteri and Mullenders, 2008).

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