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Abstract

Abstract

Nucleotide excision repair (NER) removes bulky DNA lesions from the genome. The toxic effects of these lesions relate to their potency to block replication and transcription elongation. Two mechanistically distinct NER subpathways have been identified: Global genome NER (GG-NER) and transcription-coupled repair (TC-NER). In the currently prevailing model, NER factors are sequentially assembled into pre- and post-incision complexes; however, the regulation of NER in vivo is poorly understood. I will focus on GG-NER particularly on damage recognition and mechanisms that control the transition from dual incision to repair synthesis and UV induced signalling. Moreover, we provide evidence that damage signalling in nondividing cells proceeds via NER dependent and independent UV photolesion processing. The second part of my talk deals with TC-NER in UV-irradiated cells. Deficiency in TC-NER is a hallmark of the rare human disorder Cockayne syndrome (CS). Two complementation groups (A and B) have been identified. Both CS proteins have distinct functions in recruitment of NER factors and chromatin remodelers. The emerging picture of TCR is complex: repair of transcription blocking lesions requires the NER factors, chromatin remodelers and at least two essential assembly factors, ie the CSA and B proteins. Together these, and yet unidentified proteins, will accomplish not only efficient repair thereby counteracting mutagenesis and cytoxicity but also contribute to DNA damage signalling events.

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/content/papers/10.5339/qproc.2012.mutagens.3.62
2012-03-01
2019-09-16
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http://instance.metastore.ingenta.com/content/papers/10.5339/qproc.2012.mutagens.3.62
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  • Received: 12 May 2012
  • Accepted: 12 May 2012
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