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Analysis of APOBEC-induced mutations in yeast strains with low levels of replicative DNA polymerases.

Publication ,  Journal Article
Sui, Y; Qi, L; Zhang, K; Saini, N; Klimczak, LJ; Sakofsky, CJ; Gordenin, DA; Petes, TD; Zheng, D-Q
Published in: Proc Natl Acad Sci U S A
April 28, 2020

Yeast strains with low levels of the replicative DNA polymerases (alpha, delta, and epsilon) have high levels of chromosome deletions, duplications, and translocations. By examining the patterns of mutations induced in strains with low levels of DNA polymerase by the human protein APOBEC3B (a protein that deaminates cytosine in single-stranded DNA), we show dramatically elevated amounts of single-stranded DNA relative to a wild-type strain. During DNA replication, one strand (defined as the leading strand) is replicated processively by DNA polymerase epsilon and the other (the lagging strand) is replicated as short fragments initiated by DNA polymerase alpha and extended by DNA polymerase delta. In the low DNA polymerase alpha and delta strains, the APOBEC-induced mutations are concentrated on the lagging-strand template, whereas in the low DNA polymerase epsilon strain, mutations occur on the leading- and lagging-strand templates with similar frequencies. In addition, for most genes, the transcribed strand is mutagenized more frequently than the nontranscribed strand. Lastly, some of the APOBEC-induced clusters in strains with low levels of DNA polymerase alpha or delta are greater than 10 kb in length.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

April 28, 2020

Volume

117

Issue

17

Start / End Page

9440 / 9450

Location

United States

Related Subject Headings

  • Sequence Analysis, DNA
  • Saccharomyces cerevisiae
  • Mutation
  • Minor Histocompatibility Antigens
  • Humans
  • Genome-Wide Association Study
  • Gene Expression Regulation, Fungal
  • Fungal Proteins
  • DNA-Directed DNA Polymerase
  • DNA, Fungal
 

Citation

APA
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ICMJE
MLA
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Sui, Y., Qi, L., Zhang, K., Saini, N., Klimczak, L. J., Sakofsky, C. J., … Zheng, D.-Q. (2020). Analysis of APOBEC-induced mutations in yeast strains with low levels of replicative DNA polymerases. Proc Natl Acad Sci U S A, 117(17), 9440–9450. https://doi.org/10.1073/pnas.1922472117
Sui, Yang, Lei Qi, Ke Zhang, Natalie Saini, Leszek J. Klimczak, Cynthia J. Sakofsky, Dmitry A. Gordenin, Thomas D. Petes, and Dao-Qiong Zheng. “Analysis of APOBEC-induced mutations in yeast strains with low levels of replicative DNA polymerases.Proc Natl Acad Sci U S A 117, no. 17 (April 28, 2020): 9440–50. https://doi.org/10.1073/pnas.1922472117.
Sui Y, Qi L, Zhang K, Saini N, Klimczak LJ, Sakofsky CJ, et al. Analysis of APOBEC-induced mutations in yeast strains with low levels of replicative DNA polymerases. Proc Natl Acad Sci U S A. 2020 Apr 28;117(17):9440–50.
Sui, Yang, et al. “Analysis of APOBEC-induced mutations in yeast strains with low levels of replicative DNA polymerases.Proc Natl Acad Sci U S A, vol. 117, no. 17, Apr. 2020, pp. 9440–50. Pubmed, doi:10.1073/pnas.1922472117.
Sui Y, Qi L, Zhang K, Saini N, Klimczak LJ, Sakofsky CJ, Gordenin DA, Petes TD, Zheng D-Q. Analysis of APOBEC-induced mutations in yeast strains with low levels of replicative DNA polymerases. Proc Natl Acad Sci U S A. 2020 Apr 28;117(17):9440–9450.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

April 28, 2020

Volume

117

Issue

17

Start / End Page

9440 / 9450

Location

United States

Related Subject Headings

  • Sequence Analysis, DNA
  • Saccharomyces cerevisiae
  • Mutation
  • Minor Histocompatibility Antigens
  • Humans
  • Genome-Wide Association Study
  • Gene Expression Regulation, Fungal
  • Fungal Proteins
  • DNA-Directed DNA Polymerase
  • DNA, Fungal