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Cooperative interaction between AAG and UV-DDB in the removal of modified bases

Title
Cooperative interaction between AAG and UV-DDB in the removal of modified bases
Authors
Jang S.Kumar N.Schaich M.A.Zhong Z.van Loon B.Watkins S.C.Van Houten B.
Ewha Authors
장선복
SCOPUS Author ID
장선복scopus
Issue Date
2022
Journal Title
Nucleic acids research
ISSN
1362-4962JCR Link
Citation
Nucleic acids research vol. 50, no. 22, pp. 12856 - 12871
Publisher
NLM (Medline)
Indexed
SCOPUS scopus
Document Type
Article
Abstract
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.
DOI
10.1093/nar/gkac1145
Appears in Collections:
약학대학 > 약학과 > Journal papers
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