Structural Biology of the HEAT‐Like Repeat Family of DNA Glycosylases

DNA glycosylases remove aberrant DNA nucleobases as the first enzymatic step of the base excision repair (BER) pathway. The alkyl‐DNA glycosylases AlkC and AlkD adopt a unique structure based on α‐helical HEAT repeats. Both enzymes identify and excise their substrates without a base‐flipping mechanism used by other glycosylases and nucleic acid processing proteins to access nucleobases that are otherwise stacked inside the double‐helix. Consequently, these glycosylases act on a variety of cationic nucleobase modifications, including bulky adducts, not previously associated with BER. The related non‐enzymatic HEAT‐like repeat (HLR) proteins, AlkD2, and AlkF, have unique nucleic acid binding properties that expand the functions of this relatively new protein superfamily beyond DNA repair. Here, we review the phylogeny, biochemistry, and structures of the HLR proteins, which have helped broaden our understanding of the mechanisms by which DNA glycosylases locate and excise chemically modified DNA nucleobases.

• Publication year

  2018

• Venue

  Bioessays

• Publication date

  2018-09-28

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1002/bies.201800133PMID 30264543
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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