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
Artikel, Zweitveröffentlichung, Verlagsversion
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Kurzbeschreibung (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.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2022 |
| Autor(en): | Ensminger, Michael ; Iloff, Lucie ; Ebel, Christian ; Nikolova, Teodora ; Kaina, Bernd ; Löbrich, Markus |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | DNA breaks and chromosomal aberrations arise when replication meets base excision repair |
| Sprache: | Englisch |
| Publikationsjahr: | 2022 |
| Publikationsdatum der Erstveröffentlichung: | 2014 |
| Verlag: | Rockefeller University Press |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Journal of Cell Biology |
| Jahrgang/Volume einer Zeitschrift: | 206 |
| (Heft-)Nummer: | 1 |
| DOI: | 10.26083/tuprints-00018940 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/18940 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichungsservice |
| Kurzbeschreibung (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: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-189406 |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Radiation Biology and DNA Repair |
| Hinterlegungsdatum: | 11 Mär 2022 13:04 |
| Letzte Änderung: | 14 Mär 2022 06:12 |
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| Suche nach Titel in: | TUfind oder in Google |
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