Universität zu Köln

Lans, Hannes ORCID: 0000-0003-4417-5358, Hoeijmakers, Jan H. J., Vermeulen, Wim and Marteijn, Jurgen A. (2019). The DNA damage response to transcription stress. Nat. Rev. Mol. Cell Biol., 20 (12). S. 766 - 785. LONDON: NATURE PUBLISHING GROUP. ISSN 1471-0080

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Abstract

The spatiotemporal control of RNA polymerase II (Pol II)-mediated gene transcription is tightly and intricately regulated. In addition, preservation of the integrity of the DNA template is required so as to ensure unperturbed transcription, particularly since DNA is continually challenged by different types of damaging agents that can form transcription-blocking DNA lesions (TBLs), which impede transcription elongation and cause transcription stress. To overcome the highly cytotoxic effects of TBLs, an intricate cellular response has evolved, in which the transcription-coupled nucleotide excision repair (TC-NER) pathway has a central role in removing TBLs specifically from the transcribed strand. Damage detection by stalling of the transcribing PollI is highly efficient, but a stalled Pol II complex may create an even bigger problem by interfering with repair of the lesions, and overall with transcription and replication. In this Review, we discuss the effects of different types of DNA damage on Pol II, important concepts of transcription stress, the manner in which TBLs are removed by TC-NER and how different tissues respond to TBLs. We also discuss the role of TBLs in ageing and the complex genotype-phenotype correlations of TC-NER hereditary disorders.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lans, Hannes UNSPECIFIED orcid.org/0000-0003-4417-5358 UNSPECIFIED Hoeijmakers, Jan H. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vermeulen, Wim UNSPECIFIED UNSPECIFIED UNSPECIFIED Marteijn, Jurgen A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-126405
DOI:	10.1038/s41580-019-0169-4
Journal or Publication Title:	Nat. Rev. Mol. Cell Biol.
Volume:	20
Number:	12
Page Range:	S. 766 - 785
Date:	2019
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1471-0080
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RNA-POLYMERASE-II; NUCLEOTIDE EXCISION-REPAIR; UV-SENSITIVE SYNDROME; GROUP-B PROTEIN; CYCLOBUTANE PYRIMIDINE DIMER; COCKAYNE-SYNDROME PROTEINS; STRAND BREAK REPAIR; PRE-MESSENGER-RNA; COUPLED REPAIR; XERODERMA-PIGMENTOSUM Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12640