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Disorders with Deficiency in TC-NER: Molecular Pathogenesis of Cockayne Syndrome and UV-Sensitive Syndrome

  • Chaowan Guo
  • Tomoo OgiEmail author
Chapter

Abstract

Nucleotide excision repair (NER) is one of the most important DNA repair systems involved in removing a wide range of DNA damage from the genome. NER consists of two sub-pathways: the global genome nucleotide excision repair (GG-NER) pathway, which removes DNA lesions generated in the whole genome (as described in Chap.  1 of this book), and the transcription-coupled nucleotide excision repair (TC-NER) pathway, which removes lesions specifically from the transcribed strands of actively transcribed genes. At least 20 factors are involved in the TC-NER process, and mutations in the genes responsible for coding these factors may mainly result in two human genetic disorders: Cockayne syndrome (CS) and UV-sensitive syndrome (UVSS). Despite similar molecular defects in TC-NER, CS and UVSS show distinct clinical phenotypes. CS patients display severe developmental and neurological abnormalities as well as premature ageing, whereas UVSS individuals only show milder cutaneous abnormalities, such as hypersensitivity to UV light. The molecular basis for the difference in the clinical features remains unclear. In this chapter, we will specifically describe the historical progress and recent findings of TC-NER and summarize the current understanding of the molecular pathogenesis of CS and UVSS.

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of GeneticsResearch Institute of Environmental Medicine (RIEM), Nagoya UniversityNagoyaJapan
  2. 2.Department of Human Genetics and Molecular BiologyGraduate School of Medicine, Nagoya UniversityNagoyaJapan

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