Cooperative interaction between AAG and UV-DDB in the removal of modified bases
- 등재 SCOPUS
- 발행기관 NLM (Medline)
- 발행년도 2022
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000203468
- 본문언어 영어
- Published As https://doi.org/10.1093/nar/gkac1145
- PubMed https://pubmed.ncbi.nlm.nih.gov/36511855
초록/요약
UV-DDB is a DNA damage recognition protein recently discovered to participate in the removal of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxoG) by stimulating multiple steps of base excision repair (BER). In this study, we examined whether UV-DDB has a wider role in BER besides oxidized bases and found it has specificity for two known DNA substrates of alkyladenine glycosylase (AAG)/N-methylpurine DNA glycosylase (MPG): 1, N6-ethenoadenine (ϵA) and hypoxanthine. Gel mobility shift assays show that UV-DDB recognizes these two lesions 4-5 times better than non-damaged DNA. Biochemical studies indicated that UV-DDB stimulated AAG activity on both substrates by 4- to 5-fold. Native gels indicated UV-DDB forms a transient complex with AAG to help facilitate release of AAG from the abasic site product. Single molecule experiments confirmed the interaction and showed that UV-DDB can act to displace AAG from abasic sites. Cells when treated with methyl methanesulfonate resulted in foci containing AAG and UV-DDB that developed over the course of several hours after treatment. While colocalization did not reach 100%, foci containing AAG and UV-DDB reached a maximum at three hours post treatment. Together these data indicate that UV-DDB plays an important role in facilitating the repair of AAG substrates. © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.
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