PMID:21169365

Citation	Banerjee, D, Mandal, SM, Das, A, Hegde, ML, Das, S, Bhakat, KK, Boldogh, I, Sarkar, PS, Mitra, S and Hazra, TK (2011) Preferential repair of oxidized base damage in the transcribed genes of mammalian cells. J. Biol. Chem. 286:6006-16
Abstract	Preferential repair of bulky DNA adducts from the transcribed genes via nucleotide excision repair is well characterized in mammalian cells. However, definitive evidence is lacking for similar repair of oxidized bases, the major endogenous DNA lesions. Here we show that the oxidized base-specific human DNA glycosylase NEIL2 associates with RNA polymerase II and the transcriptional regulator heterogeneous nuclear ribonucleoprotein-U (hnRNP-U), both in vitro and in cells. NEIL2 immunocomplexes from cell extracts preferentially repaired the mutagenic cytosine oxidation product 5-hydroxyuracil in the transcribed strand. In a reconstituted system, we also observed NEIL2-initiated transcription-dependent base excision repair of 5-hydroxyuracil in the transcribed strand, with hnRNP-U playing a critical role. Chromatin immunoprecipitation/reimmunoprecipitation studies showed association of NEIL2, RNA polymerase II, and hnRNP-U on transcribed but not on transcriptionally silent genes. Furthermore, NEIL2-depleted cells accumulated more DNA damage in active than in silent genes. These results strongly support the preferential role of NEIL2 in repairing oxidized bases in the transcribed genes of mammalian cells.
Links	PubMed PMC3057786 Online version:10.1074/jbc.M110.198796
Keywords	Cell-Free System; Cytosine/metabolism; DNA Adducts/genetics; DNA Adducts/metabolism; DNA Damage; DNA Glycosylases/genetics; DNA Glycosylases/metabolism; DNA Repair; DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics; DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism; HEK293 Cells; Heterogeneous-Nuclear Ribonucleoprotein U/genetics; Heterogeneous-Nuclear Ribonucleoprotein U/metabolism; Humans; Oxidation-Reduction; RNA Polymerase II/genetics; RNA Polymerase II/metabolism; Transcription, Genetic/genetics
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:NEIL2		GO:0032300: mismatch repair complex	ECO:0000314:		C		Figure 4A	complete CACAO 11774

References

See Help:References for how to manage references in GONUTS.