Mechanisms of global and region-specific control of mutagenesis

Youri I. Pavlov, Artem G. Lada, Corinn Grabow, Elena I. Stepchenkova

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Scopus citations


The rate of mutations in each site of a eukaryotic genome depends on a plethora of factors: nucleotides pools, asymmetry and timing of replication, types of DNA damage and parameters of its repair, translesion DNA synthesis and structure of chromatin. Studies of mutation mechanisms, traditionally performed with model systems, are currently boosted by revolutionary analysis of mutation landscapes of cancer genomes. Etiology of familial and sporadic cancers is connected to mutations in DNA and mismatch genes that unevenly lower the accuracy of replication in different chromosomal regions. Transient appearance of single-stranded DNA makes some genomic sites vulnerable to spontaneous or enzymatic deamination by AID/APOBECs that lead to clustered mutations called kataegis. Of special significance is an impact of cell ploidy on mutagenesis outcomes. Haploid cells with the highest levels of mutagenesis die due to lethal mutations. Descendants of hypermutable cells in diploids, where lethal recessive mutations load is tolerated, could be recovered and analyzed, permitting a glimpse into hitherto hidden mechanisms of mutagenesis.

Original languageEnglish (US)
Title of host publicationGenetics, Evolution and Radiation
Subtitle of host publicationCrossing Borders, The Interdisciplinary Legacy of Nikolay W. Timofeeff-Ressovsky
PublisherSpringer International Publishing
Number of pages22
ISBN (Electronic)9783319488387
ISBN (Print)9783319488370
StatePublished - Jan 1 2017


  • Cancer
  • DNA polymerases
  • Editing AID/APOBEC deaminases
  • Evolution
  • Kataegis
  • Mutagens
  • Mutation hot spots
  • Nucleotide pools
  • Recombination
  • Repair
  • Replication
  • Transcription

ASJC Scopus subject areas

  • General Agricultural and Biological Sciences
  • General Engineering
  • General Environmental Science
  • General Medicine
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


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