Biotin requirements for DNA damage prevention

Janos Zempleni, Daniel Camara Teixeira, Toshinobu Kuroishi, Elizabeth L. Cordonier, Scott Baier

Research output: Contribution to journalReview article

16 Scopus citations

Abstract

Biotin serves as a covalently bound coenzyme in five human carboxylases; biotin is also attached to histones H2A, H3, and H4, although the abundance of biotinylated histones is low. Biotinylation of both carboxylases and histones is catalyzed by holocarboxylase synthetase. Human biotin requirements are unknown. Recommendations for adequate intake of biotin are based on the typical intake of biotin in an apparently healthy population, which is only a crude estimate of the true intake due to analytical problems. Importantly, intake recommendations do not take into account possible effects of biotin deficiency on impairing genome stability. Recent studies suggest that biotin deficiency causes de-repression of long terminal repeats, thereby causing genome instability. While it was originally proposed that these effects are caused by loss of biotinylated histones, more recent evidence suggests a more immediate role of holocarboxylase synthetase in forming multiprotein complexes in chromatin that are important for gene repression. Holocarboxylase synthetase appears to interact physically with the methyl-CpG-binding domain protein 2 and, perhaps, histone methyl transferases, thereby creating epigenetic synergies between biotinylation and methylation events. These observations might offer a mechanistic explanation for some of the birth defects seen in biotin-deficient animal models.

Original languageEnglish (US)
Pages (from-to)58-60
Number of pages3
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume733
Issue number1-2
DOIs
StatePublished - May 1 2012

Keywords

  • Biotin
  • Epigenetics
  • Genome stability
  • Human
  • Requirements

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

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