Stem cells, one of the progenitors of cancer, exist predominately in a quiescent 
state. Thus, understanding the mechanisms of DNA repair and mutagenesis in such 
arrested cells may help unravel the complex process of tumorigenesis. Two major 
nucleotide excision repair (NER) pathways are known to remove bulky physical or 
chemical lesions from DNA. Transcription-coupled repair (TCR) acts solely on the 
transcribed strand of expressed genes, while global genomic repair (GGR) is 
responsible for the ubiquitous repair of the genome. Indirectly, it has been 
shown that while TCR functions in quiescent cells GGR does not. To explicitly 
elucidate this phenomenon, we adapted a quantitative PCR (QPCR) assay to study 
UV-damage repair via TCR and GGR in quiescent and proliferating cells. We 
present evidence that repair of untranscribed silent regions of the genome and 
repair of the non-transcribed strand of active genes proceeds by two discrete 
mechanisms in quiescent cells; rather than by GGR, which was believed to 
encompass both. Thus, our findings suggest the existence of an alternate NER 
pathway in quiescent cells. The proposed subcategories of NER are as follows: 
(i) TCR, responsible for maintenance of transcribed strands; (ii) GGR, 
responsible for ubiquitous genome repair; and (iii) non-transcribed strand 
repair (NTSR), predominantly responsible for the repair of the NTS in arrested 
cells. In quiescent cells, it is evident that TCR and NTSR function and GGR are 
arrested. As a consequence, mutation accumulation at temporally silent genes and 
incomplete or imperfect repair of transcribed genes, in quiescent stem cells, 
may provide a source of cancer causing mutations.