Mutator effects and mutation signatures of editing deaminases produced in bacteria and yeast

A. G. Lada, C. Frahm Krick, S. G. Kozmin, V. I. Mayorov, T. S. Karpova, I. B. Rogozin, Youri I Pavlov

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Enzymatic deamination of bases in DNA or RNA leads to an alteration of flow of genetic information. Adenosine deaminases edit RNA (ADARs, TADs). Specialized cytidine deaminases are involved in RNA/DNA editing in lipid metabolism (APOBEC1) and in innate (APOBEC3 family) and humoral (AID) immunity. APOBEC2 is required for proper muscle development and, along with AID, was implicated in demethylation of DNA. The functions of APOBEC4, APOBEC5, and other deaminases recently discovered by bioinformatics approaches are unknown. What is the basis for the diverse biological functions of enzymes with similar enzyme structure and the same principal enzymatic reaction? AID, APOBEC1, lamprey CDA1, and APOBEC3G enzymes cause uracil DNA glycosylase-dependent induction of mutations when overproduced ectopically in bacteria or yeast. APOBEC2, on the contrary, is nonmutagenic. We studied the effects of the expression of various deaminases in yeast and bacteria. The mutagenic specificities of four deaminases, hAID, rAPOBEC1, hAPOBEC3G, and lamprey CDA1, are strikingly different. This suggests the existence of an intrinsic component of deaminase targeting. The expression of yeast CDD1 and TAD2/TAD3, human APOBEC4, Xanthomonas oryzae APOBEC5, and deaminase encoded by Micromonas sp. gene MICPUN-56782 was nonmutagenic. A lack of a mutagenic effect for Cdd1 is expected because the enzyme functions in the salvage of pyrimidine nucleotides, and it is evolutionarily distant from RNA/DNA editing enzymes. The reason for inactivity of deaminases grouped with APOBEC2 is not obvious from their structures. This cannot be explained by protein insolubility and peculiarities of cellular distribution and requires further investigation.

Original languageEnglish (US)
Pages (from-to)131-146
Number of pages16
JournalBiochemistry (Moscow)
Volume76
Issue number1
DOIs
Publication statusPublished - Jan 1 2011

    Fingerprint

Keywords

  • DNA repair
  • editing deaminases
  • immunity
  • mutagenesis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Lada, A. G., Frahm Krick, C., Kozmin, S. G., Mayorov, V. I., Karpova, T. S., Rogozin, I. B., & Pavlov, Y. I. (2011). Mutator effects and mutation signatures of editing deaminases produced in bacteria and yeast. Biochemistry (Moscow), 76(1), 131-146. https://doi.org/10.1134/S0006297911010135