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. 2010 Jul;30(13):3206-15.
doi: 10.1128/MCB.00308-10. Epub 2010 Apr 26.

Abasic sites in the transcribed strand of yeast DNA are removed by transcription-coupled nucleotide excision repair

Nayun Kim  1 , Sue Jinks-Robertson
Affiliations

Abasic sites in the transcribed strand of yeast DNA are removed by transcription-coupled nucleotide excision repair

Nayun Kim et al. Mol Cell Biol. 2010 Jul.

Abstract

Abasic (AP) sites are potent blocks to DNA and RNA polymerases, and their repair is essential for maintaining genome integrity. Although AP sites are efficiently dealt with through the base excision repair (BER) pathway, genetic studies suggest that repair also can occur via nucleotide excision repair (NER). The involvement of NER in AP-site removal has been puzzling, however, as this pathway is thought to target only bulky lesions. Here, we examine the repair of AP sites generated when uracil is removed from a highly transcribed gene in yeast. Because uracil is incorporated instead of thymine under these conditions, the position of the resulting AP site is known. Results demonstrate that only AP sites on the transcribed strand are efficient substrates for NER, suggesting the recruitment of the NER machinery by an AP-blocked RNA polymerase. Such transcription-coupled NER of AP sites may explain previously suggested links between the BER pathway and transcription.

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Figures

FIG. 1.
FIG. 1.
pTET-lys2ΔA746 reversion spectra. Only the first 130 nucleotides (nt) of the reversion window are shown, as no mutations were outside of this region. The position of the adenine deleted to create the frameshift allele is indicated by a dash within the sequence. Simple insertions and deletions are indicated below the sequence by a plus sign (1-nt addition), −2, −5, etc.; complex insertions and deletions (cins and cdel, respectively) are indicated above the sequence. Complex mutations at the 6A hot spot associated with a T→G transversion (type I events) are highlighted in yellow, and those associated with an A→C transversion (type II events) are highlighted in pink. Type III events are highlighted in green. N is the number of independent revertants sequenced.
FIG. 2.
FIG. 2.
Models for generating type I and type II complex mutations in the pTET-lys2DA746 reversion assay. The starting duplex is in gray, and all newly synthesized DNA is in black. Relevant bases are highlighted in yellow. O indicates the AP site. See the text for details.
FIG. 3.
FIG. 3.
Model for the differential repair of AP sites on the TS and NTS of active genes. See the text for details.
See this image and copyright information in PMC

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