Acetylation of the human DNA glycosylase NEIL2 and inhibition of its activity.
Post-translational modifications of proteins, including acetylation, modulate their cellular functions. Several human DNA replication and repair enzymes have recently been shown to be acetylated, leading to their inactivation in some cases. Here we show that the transcriptional coactivator p300 stably interacts with, and acetylates, the recently discovered human DNA glycosylase NEIL2, involved in the repair of oxidized bases both in vivo and in vitro. Lys49 and Lys153 were identified as the major acetylation sites in NEIL2. Acetylation of Lys49, conserved among Nei orthologs, or its mutation to Arg inactivates both base excision and AP lyase activities, while acetylation of Lys153 has no effect. Reversible acetylation of Lys49 could thus regulate the repair activity of NEIL2 in vivo.
Bhakat
Kishor K
KK
Sealy Center for Molecular Science and Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, TX 77555-1079, USA.
Hazra
Tapas K
TK
Mitra
Sankar
S
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D045647:DNA Glycosylases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D051548:Histone Acetyltransferases; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011233:Precipitin Tests; D011485:Protein Binding; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D045647:DNA Glycosylases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D051548:Histone Acetyltransferases; D008239:Lysine; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C473642:NEIL2 protein, human