Timing of DNA lesion recognition: Ubiquitin signaling in the NER pathway

ABSTRACT

Damaged DNA is repaired by specialized repair factors that are recruited in a well-orchestrated manner to the damage site. The DNA damage response at UV inflicted DNA lesions is accompanied by posttranslational modifications of DNA repair factors and the chromatin environment sourrounding the lesion. In particular, mono- and poly-ubiquitylation events are an integral part of the DNA damage signaling. Whereas ubiquitin signaling at DNA doublestrand breaks has been subject to intensive studies comparatively little is known about the intricacies of ubiquitylation events occurring during nucleotide excision repair (NER), the major pathway to remove bulky helix lesions. Both, the global genomic (GG-NER) and the transcription-coupled (TC-NER) branches of NER are subject to ubiquitylation and deubiquitylation processes.Here we summarize our current knowledge of the ubiquitylation network that drives DNA repair in the NER pathway and we discuss the crosstalk of ubiquitin signaling with other prominent post-translational modfications that might be essential to time the DNA damage recognition step.

KEYWORDS:

• de-ubiquitylation
• DNA damage response
• nucleotide excision repair
• mono-ubiquitylation
• poly-ubiquitylation
• ubiquitin

Abbreviations

DDR	=	DNA damage response
DSB	=	double strand breaks
NER	=	nucleotide excision repair
GG-NER	=	global genomic nucleotide excision repair
TC-NER	=	transcription coupled nucleotide excision repair
UV	=	ultraviolet
CDP	=	cyclopyrimidine dimer
Pol II	=	RNA Polymerase II

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thank members of the Richly laboratory for critical reading of the manuscript. We apologize to colleagues for being unable to cite their work due to space limitations.

Funding

H.R is supported by grants from the Boehringer Ingelheim Foundation.