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J Mol Biol. 2017 Oct 27;429(21):3146-3155. doi: 10.1016/j.jmb.2016.11.006. Epub 2016 Nov 13.

Traveling Rocky Roads: The Consequences of Transcription-Blocking DNA Lesions on RNA Polymerase II.

Author information

1
Department of Molecular Genetics, Erasmus MC, Wytemaweg 80, Rotterdam 3015 CN, The Netherlands.
2
Department of Molecular Genetics, Erasmus MC, Wytemaweg 80, Rotterdam 3015 CN, The Netherlands. Electronic address: J.Marteijn@erasmusmc.nl.

Abstract

The faithful transcription of eukaryotic genes by RNA polymerase II (RNAP2) is crucial for proper cell function and tissue homeostasis. However, transcription-blocking DNA lesions of both endogenous and environmental origin continuously challenge the progression of elongating RNAP2. The stalling of RNAP2 on a transcription-blocking lesion triggers a series of highly regulated events, including RNAP2 processing to make the lesion accessible for DNA repair, R-loop-mediated DNA damage signaling, and the initiation of transcription-coupled DNA repair. The correct execution and coordination of these processes is vital for resuming transcription following the successful repair of transcription-blocking lesions. Here, we outline recent insights into the molecular consequences of RNAP2 stalling on transcription-blocking DNA lesions and how these lesions are resolved to restore mRNA synthesis.

KEYWORDS:

DNA damage; RNA polymerase 2; nucleotide excision repair; transcription coupled repair; transcription restart

PMID:
27851891
DOI:
10.1016/j.jmb.2016.11.006
[Indexed for MEDLINE]
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