Ensminger, Michael ; Iloff, Lucie ; Ebel, Christian ; Nikolova, Teodora ; Kaina, Bernd ; Löbrich, Markus (2014)
DNA breaks and chromosomal aberrations arise when replication meets base excision repair.
In: The Journal of cell biology, 206 (1)
Artikel, Bibliographie
Dies ist die neueste Version dieses Eintrags.
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: | 2014 |
| Autor(en): | Ensminger, Michael ; Iloff, Lucie ; Ebel, Christian ; Nikolova, Teodora ; Kaina, Bernd ; Löbrich, Markus |
| Art des Eintrags: | Bibliographie |
| Titel: | DNA breaks and chromosomal aberrations arise when replication meets base excision repair. |
| Sprache: | Englisch |
| Publikationsjahr: | 2014 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | The Journal of cell biology |
| Jahrgang/Volume einer Zeitschrift: | 206 |
| (Heft-)Nummer: | 1 |
| Zugehörige Links: | |
| 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. |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Radiation Biology and DNA Repair |
| Hinterlegungsdatum: | 11 Sep 2014 08:22 |
| Letzte Änderung: | 03 Jul 2024 02:21 |
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| Suche nach Titel in: | TUfind oder in Google |
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DNA breaks and chromosomal aberrations arise when replication meets base excision repair. (deposited 11 Mär 2022 13:04)
- DNA breaks and chromosomal aberrations arise when replication meets base excision repair. (deposited 11 Sep 2014 08:22) [Gegenwärtig angezeigt]
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