Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: In vivo repair of methylation damage in Aag 3-methyladenine DNA glycosylase null mouse cells.

Authors: Smith, S A; Engelward, B P

Published In Nucleic Acids Res, (2000 Sep 01)

Abstract: 3-Methyladenine (3MeA) DNA glycosylases initiate base excision repair by removing 3MeA. These glycosylases also remove a broad spectrum of spontaneous and environmentally induced base lesions in vitro. Mouse cells lacking the Aag 3MeA DNA glycosylase (also known as the Mpg, APNG or ANPG DNA glycosylase) are susceptible to 3MeA-induced S phase arrest, chromosome aberrations and apoptosis, but it is not known if Aag is solely responsible for repair of 3MeA in vivo. Here we show that in AAG:(-/-) cells, 3MeA lesions disappear from the genome slightly faster than would be expected by spontaneous depurination alone, suggesting that there may be residual repair of 3MeA. However, repair of 3MeA is at least 10 times slower in AAG:(-/-) cells than in AAG:(+/+) cells. Consequently, 24 h after exposure to [(3)H]MNU, 30% of the original 3MeA burden is intact in AAG:(-/-) cells, while 3MeA is undetectable in AAG:(+/+) cells. Thus, Aag is the major DNA glycosylase for 3MeA repair. We also investigated the in vivo repair kinetics of another Aag substrate, 7-methylguanine. Surprisingly, 7-methylguanine is removed equally efficiently in AAG:(+/+) and AAG:(-/-) cells, suggesting that another DNA glycosylase acts on lesions previously thought to be repaired by Aag.

PubMed ID: 10954597 Exiting the NIEHS site

MeSH Terms: Adenine/analogs & derivatives*; Adenine/chemistry; Adenine/metabolism; Animals; Cell Line; DNA Adducts/chemistry; DNA Adducts/drug effects; DNA Adducts/genetics; DNA Adducts/metabolism*; DNA Damage/drug effects; DNA Damage/genetics*; DNA Glycosylases*; DNA Methylation*; DNA Repair/genetics*; DNA Replication/drug effects; Gene Deletion; Genotype; Guanine/analogs & derivatives*; Guanine/metabolism; Guanosine/analogs & derivatives*; Guanosine/genetics; Guanosine/metabolism; Methylnitrosourea/toxicity; Mice; Mice, Knockout; N-Glycosyl Hydrolases/deficiency*; N-Glycosyl Hydrolases/genetics; N-Glycosyl Hydrolases/metabolism*

Back
to Top