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The human DNA glycosylases NEIL1 and NEIL3 excise psoralen-induced DNA-DNA cross-links in a four-stranded DNA structure

Martin, PR; Couve, S; Zutterling, C; Albelazi, MS; Groisman, R; Matkarimov, BT; Parsons, JL; Elder, RH; Saparbaev, MS

The human DNA glycosylases NEIL1 and NEIL3 excise psoralen-induced DNA-DNA cross-links in a four-stranded DNA structure Thumbnail


Authors

PR Martin

S Couve

C Zutterling

MS Albelazi

R Groisman

BT Matkarimov

JL Parsons

RH Elder

MS Saparbaev



Abstract

Interstrand cross-links (ICLs) are highly cytotoxic DNA lesions that block DNA replication and transcription by preventing strand separation. Previously, we demonstrated that the bacterial and
human DNA glycosylases Nei and NEIL1 excise unhooked psoralen-derived ICLs in three-stranded DNA via hydrolysis of the glycosidic bond between the crosslinked base and deoxyribose sugar. Furthermore, NEIL3 from Xenopus laevis has been shown to cleave psoralen- and abasic site-induced ICLs in Xenopus
egg extracts. Here we report that human NEIL3 cleaves psoralen-induced DNA-DNA cross-links in three-stranded and four-stranded DNA substrates to generate unhooked DNA fragments containing
either an abasic site or a psoralen-thymine monoadduct. Furthermore, while Nei and NEIL1 also cleave a psoralen-induced four-stranded DNA substrate to generate two unhooked DNA duplexes with a nick, NEIL3 targets both DNA strands in the ICL without generating single-strand breaks. The DNA substrate specificities of these Nei-like enzymes imply the occurrence of long uninterrupted three- and four-stranded crosslinked DNA-DNA structures that may originate in vivo from DNA replication fork
bypass of an ICL. In conclusion, the Nei-like DNA glycosylases unhook psoralen-derived ICLs in various DNA structures via a genuine repair mechanism in which complex DNA lesions can be removed without generation of highly toxic double-strand breaks.

Citation

Martin, P., Couve, S., Zutterling, C., Albelazi, M., Groisman, R., Matkarimov, B., …Saparbaev, M. (2017). The human DNA glycosylases NEIL1 and NEIL3 excise psoralen-induced DNA-DNA cross-links in a four-stranded DNA structure. Scientific reports, 7(17438), https://doi.org/10.1038/s41598-017-17693-4

Journal Article Type Article
Acceptance Date Nov 29, 2017
Online Publication Date Dec 12, 2017
Publication Date Dec 12, 2017
Deposit Date Dec 12, 2017
Publicly Available Date Dec 12, 2017
Journal Scientific Reports
Print ISSN 2045-2322
Electronic ISSN 2045-2322
Publisher Nature Publishing Group
Volume 7
Issue 17438
DOI https://doi.org/10.1038/s41598-017-17693-4
Publisher URL http://dx.doi.org/10.1038/s41598-017-17693-4
Related Public URLs https://www.nature.com/srep/
Additional Information Funders : la Ligue Nationale Française Contre le Cancer;North West Cancer Research

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