A new structural DNA glycosylase containing HEAT-like repeats
This domain represents a new and uncharacterized structural superfamily of DNA glycosylases that form an alpha-alpha superhelix fold that are not belong to the identified five structural DNA glycosylase superfamilies (UDG, AAG/MNPG, MutM/Fpg and helix-hairpin-helix). DNA glycosylases removing alkylated base residues have been identified in all organisms investigated and may be universally present in nature. DNA glycosylases catalyze the first step in Base Excision Repair (BER) pathway by cleaving damaged DNA bases within double strand DNA to produce an abasic site. The resulting abasic site is further processed by AP endonuclease, phosphodiesterase, DNA polymerases, and DNA ligase functions to restore the DNA to an undamaged state. All glycosylase examined to date utilize a similar strategy for binding DNA and base flipping despite their structural diversity. The known structures for members of this family, AlkC and AlkD from Bacillus cereus, are distant homologues and are composed of six variant HEAT (Huntington/Elongation/ A subunit/Target of rapamycin) repeats. HEAT motifs are ~45-amino acid sequences that form antiparallel alpha-helices, which are packed by a conserved hyrophobic interface and are tandemly repeated to form superhelical alpha-structures. AlkD and AlkC are specific for removal of 3-methyladenine (3mA) and 7-methylguanine (7mG) from the DNA by base excision repair. Homologues of AlkC and AlkD were also identified in other organisms.