Ensminger, Michael ; Iloff, Lucie ; Ebel, Christian ; Nikolova, Teodora ; Kaina, Bernd ; Löbrich, Markus (2022)
DNA breaks and chromosomal aberrations arise when replication meets base excision repair.
In: Journal of Cell Biology, 2014, 206 (1)
doi: 10.26083/tuprints-00018940
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Item Type: | Article |
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Type of entry: | Secondary publication |
Title: | DNA breaks and chromosomal aberrations arise when replication meets base excision repair |
Language: | English |
Date: | 2022 |
Place of Publication: | Darmstadt |
Year of primary publication: | 2014 |
Publisher: | Rockefeller University Press |
Journal or Publication Title: | Journal of Cell Biology |
Volume of the journal: | 206 |
Issue Number: | 1 |
DOI: | 10.26083/tuprints-00018940 |
Corresponding Links: | |
Origin: | Secondary publication service |
Abstract: | Exposures that methylate DNA potently induce DNA double-strand breaks (DSBs) and chromosomal aberrations, which are thought to arise when damaged bases block DNA replication. Here, we demonstrate that DNA methylation damage causes DSB formation when replication interferes with base excision repair (BER), the predominant pathway for repairing methylated bases. We show that cells defective in the N-methylpurine DNA glycosylase, which fail to remove N-methylpurines from DNA and do not initiate BER, display strongly reduced levels of methylation-induced DSBs and chromosomal aberrations compared with wild-type cells. Also, cells unable to generate single-strand breaks (SSBs) at apurinic/apyrimidinic sites do not form DSBs immediately after methylation damage. In contrast, cells deficient in x-ray cross-complementing protein 1, DNA polymerase β, or poly (ADP-ribose) polymerase 1 activity, all of which fail to seal SSBs induced at apurinic/apyrimidinic sites, exhibit strongly elevated levels of methylation-induced DSBs and chromosomal aberrations. We propose that DSBs and chromosomal aberrations after treatment with N-alkylators arise when replication forks collide with SSBs generated during BER. |
Status: | Publisher's Version |
URN: | urn:nbn:de:tuda-tuprints-189406 |
Classification DDC: | 500 Science and mathematics > 570 Life sciences, biology |
Divisions: | 10 Department of Biology > Radiation Biology and DNA Repair |
Date Deposited: | 11 Mar 2022 13:04 |
Last Modified: | 14 Mar 2023 11:16 |
URI: | https://tuprints.ulb.tu-darmstadt.de/id/eprint/18940 |
PPN: | 505746026 |
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