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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Sui, Y; Qi, L; Zhang, K; Saini, N; Klimczak, LJ; Sakofsky, CJ; Gordenin, DA; Petes, TD; Zheng, D-Q

Published Date

  • April 28, 2020

Published In

Volume / Issue

  • 117 / 17

Start / End Page

  • 9440 - 9450

PubMed ID

  • 32277034

Pubmed Central ID

  • 32277034

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1922472117

Language

  • eng

Conference Location

  • United States