Unscheduled DNA synthesis leads to elevated uracil residues at highly transcribed genomic loci in Saccharomyces cerevisiae

PLoS Genetics
Norah OwitiNayun Kim

Abstract

Recombination and mutagenesis are elevated by active transcription. The correlation between transcription and genome instability is largely explained by the topological and structural changes in DNA and the associated physical obstacles generated by the transcription machinery. However, such explanation does not directly account for the unique types of mutations originating from the non-canonical residues, uracil or ribonucleotide, which are also elevated at highly transcribed regions. Based on the previous findings that abasic (AP) lesions derived from the uracil residues incorporated into DNA in place of thymine constitute a major component of the transcription-associated mutations in yeast, we formed the hypothesis that DNA synthesis ensuing from the repair of the transcription-induced DNA damage provide the opportunity for uracil-incorporation. In support of this hypothesis, we show here the positive correlation between the level of transcription and the density of uracil residues in the yeast genome indirectly through the mutations generated by the glycosylase that excise undamaged cytosine as well as uracil. The higher uracil-density at actively transcribed regions is confirmed by the long-amplicon PCR analysis. We also s...Continue Reading

References

Mar 26, 1991·Biochimica Et Biophysica Acta·N Heintz
Sep 12, 1972·Biochemistry·T Lindahl, B Nyberg
May 1, 1971·Journal of Bacteriology·R K Herman, N B Dworkin
Jan 1, 1994·Annual Review of Biochemistry·B Demple, L Harrison
Aug 14, 1998·Molecular Cell·R J ChoR W Davis
Mar 15, 2000·Nature·M M CoxK J Marians
Nov 1, 2000·The Journal of Biological Chemistry·L PostowN R Cozzarelli
Feb 2, 2002·The EMBO Journal·Andrés Aguilera
Jun 4, 2002·Nature Reviews. Molecular Cell Biology·James C Wang
Nov 26, 2002·Journal of Bacteriology·Joanna Klapacz, Ashok S Bhagwat
May 2, 2003·Nature Reviews. Cancer·Daniel B LongleyPatrick G Johnston
Jun 5, 2003·Genes & Development·Yasushi TakeuchiTakehiko Kobayashi
Aug 9, 2003·Nucleic Acids Research. Supplement·Chie OtsukaKazuo Negishi
Oct 31, 2003·Molecular and Cellular Biology·Marie Guillet, Serge Boiteux
Nov 30, 2005·Proceedings of the National Academy of Sciences of the United States of America·Paul AuerbachBruce Demple
May 6, 2006·Methods in Molecular Biology·Janine H SantosBennett Van Houten
Apr 3, 2007·DNA Repair·Christian J RudolphRobert G Lloyd
Feb 21, 2009·The FEBS Journal·Susana M Cerritelli, Robert J Crouch
Mar 5, 2009·Microbiology and Molecular Biology Reviews : MMBR·Lauren S WatersGraham C Walker
May 19, 2009·Nature·Nayun Kim, Sue Jinks-Robertson
Feb 4, 2010·Methods : a Companion to Methods in Enzymology·Senyene E HunterJoel N Meyer
Aug 24, 2010·Nature Chemical Biology·Stephanie A Nick McElhinnyThomas A Kunkel
Dec 15, 2010·Nature Immunology·Robert W MaulPatricia J Gearhart
Jun 28, 2011·Science·Nayun KimSue Jinks-Robertson

❮ Previous
Next ❯

Citations

Dec 19, 2019·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Michelle L HulkeAmnon Koren
Oct 18, 2018·Current Genetics·Norah OwitiNayun Kim

❮ Previous
Next ❯

Methods Mentioned

BETA
deamination
PCR
glycosylase

Software Mentioned

Image Lab

Related Concepts

Related Feeds