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RNA polymerase between lesion bypass and DNA repair

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Abstract

DNA damage leads to heritable changes in the genome via DNA replication. However, as the DNA helix is the site of numerous other transactions, notably transcription, DNA damage can have diverse repercussions on cellular physiology. In particular, DNA lesions have distinct effects on the passage of transcribing RNA polymerases, from easy bypass to almost complete block of transcription elongation. The fate of the RNA polymerase positioned at a lesion is largely determined by whether the lesion is structurally subtle and can be accommodated and eventually bypassed, or bulky, structurally distorting and requiring remodeling/complete dissociation of the transcription elongation complex, excision, and repair. Here we review cellular responses to DNA damage that involve RNA polymerases with a focus on bacterial transcription-coupled nucleotide excision repair and lesion bypass via transcriptional mutagenesis. Emphasis is placed on the explosion of new structural information on RNA polymerases and relevant DNA repair factors and the mechanistic models derived from it.

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Abbreviations

TC-NER:

Transcription-coupled nucleotide excision repair

GG-NER:

Global genome nucleotide excision repair

RNAP:

RNA polymerase

TM:

Transcriptional mutagenesis

TEC:

Transcription elongation complex

SAXS:

Small-angle X-ray scattering

TRCF:

Transcription-repair coupling factor

TRG:

Translocation in RecG

RH:

Relay helix

TAM:

Transcription-associated mutagenesis

NTD:

N-terminal domain

CTD:

C-terminal domain

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Acknowledgments

The author would like to thank Dr. N. Grigorieff and the Damon Runyon Cancer Research Foundation (DRG-1966-08) for support, Dr. Peter Lewis for the coordinates of the NusA-TEC model, and Dr. R. Edayathumangalam for critical reading of the manuscript.

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  1. Rosenstiel Basic Medical Sciences Research Center, Brandeis University, 415 South St., MS029, Waltham, MA, 02454, USA

    Alexandra M. Deaconescu

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Deaconescu, A.M. RNA polymerase between lesion bypass and DNA repair. Cell. Mol. Life Sci. 70, 4495–4509 (2013). https://doi.org/10.1007/s00018-013-1384-3

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