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Review
. 2013 Aug 1;5(8):a012625.
doi: 10.1101/cshperspect.a012625.

Mammalian transcription-coupled excision repair

Wim Vermeulen  1 , Maria Fousteri
Affiliations
Review

Mammalian transcription-coupled excision repair

Wim Vermeulen et al. Cold Spring Harb Perspect Biol. .

Abstract

Transcriptional arrest caused by DNA damage is detrimental for cells and organisms as it impinges on gene expression and thereby on cell growth and survival. To alleviate transcriptional arrest, cells trigger a transcription-dependent genome surveillance pathway, termed transcription-coupled nucleotide excision repair (TC-NER) that ensures rapid removal of such transcription-impeding DNA lesions and prevents persistent stalling of transcription. Defective TC-NER is causatively linked to Cockayne syndrome, a rare severe genetic disorder with multisystem abnormalities that results in patients' death in early adulthood. Here we review recent data on how damage-arrested transcription is actively coupled to TC-NER in mammals and discuss new emerging models concerning the role of TC-NER-specific factors in this process.

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Figures

Figure 1.
Figure 1.
The devastating progression of Cockayne syndrome. Pictures of the family photo album of the CS patient Baptiste, who died at the age of 10 years old.
Figure 2.
Figure 2.
Model of mammalian TC-NER. (A) During transcription elongation RNAPII travels along with CSB as well as UVSSA/USP7 complex. (B) The progression of such transcribing polymerases may be impaired by DNA lesions that prevent forward translocation of the transcription machinery resulting in RNAPII stalling or arrest and stabilization of the CSB/RNAPII interaction. This results in the assembly of UVSSA/USP7 complex at the damaged site protecting CSB from untimely degradation events. (C) CSB triggers the recruitment of the CRL4CSA complex and orchestrates the events that are required to couple the arrested RNAPII complex to chromatin remodeling events, mRNA splicing and NER. These remodeling events, mediated by p300 and HMGN1, are likely to occur upstream of the stalled RNAPII thus enabling RNAPII backtracking and assembly of the NER core machinery on both sides of the damage. Removal of the damage promotes cleavage of the protruding 3′ mRNA (possibly stimulated by TFIIS) and resumption of transcription.
See this image and copyright information in PMC

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