Mammalian ALKBH1 serves as an N⁶-mA demethylase of unpairing DNA.

ABSTRACT: N⁶-methyladenine (N⁶-mA) of DNA is an emerging epigenetic mark in mammalian genome. Levels of N⁶-mA undergo drastic fluctuation during early embryogenesis, indicative of active regulation. Here we show that the 2-oxoglutarate-dependent oxygenase ALKBH1 functions as a nuclear eraser of N⁶-mA in unpairing regions (e.g., SIDD, Stress-Induced DNA Double Helix Destabilization regions) of mammalian genomes. Enzymatic profiling studies revealed that ALKBH1 prefers bubbled or bulged DNAs as substrate, instead of single-stranded (ss-) or double-stranded (ds-) DNAs. Structural studies of ALKBH1 revealed an unexpected "stretch-out" conformation of its "Flip1" motif, a conserved element that usually bends over catalytic center to facilitate substrate base fl

SUBMITTER: Zhang M 

PROVIDER: S-EPMC7054317 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature