dc.contributor.author | Jang, Sunbok | |
dc.contributor.author | Kumar, Namrata | |
dc.contributor.author | Schaich, Mathew A. | |
dc.contributor.author | Zhong, Zhou | |
dc.contributor.author | van Loon, Barbara | |
dc.contributor.author | Watkins, Simon C. | |
dc.contributor.author | Van Houten, Bennett | |
dc.date.accessioned | 2023-02-09T06:45:45Z | |
dc.date.available | 2023-02-09T06:45:45Z | |
dc.date.created | 2023-01-19T12:34:09Z | |
dc.date.issued | 2022 | |
dc.identifier.citation | Nucleic Acids Research (NAR). 2022, 50 (22), 12856-12871. | en_US |
dc.identifier.issn | 0305-1048 | |
dc.identifier.uri | https://hdl.handle.net/11250/3049453 | |
dc.description.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. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Oxford University Press | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | Cooperative interaction between AAG and UV-DDB in the removal of modified bases | en_US |
dc.title.alternative | Cooperative interaction between AAG and UV-DDB in the removal of modified bases | en_US |
dc.type | Peer reviewed | en_US |
dc.type | Journal article | en_US |
dc.description.version | publishedVersion | en_US |
dc.source.pagenumber | 12856-12871 | en_US |
dc.source.volume | 50 | en_US |
dc.source.journal | Nucleic Acids Research (NAR) | en_US |
dc.source.issue | 22 | en_US |
dc.identifier.doi | 10.1093/nar/gkac1145 | |
dc.identifier.cristin | 2110296 | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |