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DNA Double-Strand Break Resection Occurs during Non-homologous End Joining in G1 but Is Distinct from Resection during Homologous Recombination

Biehs, Ronja ; Steinlage, Monika ; Barton, Olivia ; Juhász, Szilvia ; Künzel, Julia ; Spies, Julian ; Shibata, Atsushi ; Jeggo, Penny A. ; Löbrich, Markus (2021)
DNA Double-Strand Break Resection Occurs during Non-homologous End Joining in G1 but Is Distinct from Resection during Homologous Recombination.
In: Molecular Cell, 2017, 65 (4)
doi: 10.26083/tuprints-00013323
Artikel, Zweitveröffentlichung, Verlagsversion

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Kurzbeschreibung (Abstract)

Canonical non-homologous end joining (c-NHEJ) repairs DNA double-strand breaks (DSBs) in G1 cells with biphasic kinetics. We show that DSBs repaired with slow kinetics, including those localizing to heterochromatic regions or harboring additional lesions at the DSB site, undergo resection prior to repair by c-NHEJ and not alt-NHEJ. Resection-dependent c-NHEJ represents an inducible process during which Plk3 phosphorylates CtIP, mediating its interaction with Brca1 and promoting the initiation of resection. Mre11 exonuclease, EXD2, and Exo1 execute resection, and Artemis endonuclease functions to complete the process. If resection does not commence, then repair can ensue by c-NHEJ, but when executed, Artemis is essential to complete resection-dependent c-NHEJ. Additionally, Mre11 endonuclease activity is dispensable for resection in G1. Thus, resection in G1 differs from the process in G2 that leads to homologous recombination. Resection-dependent c-NHEJ significantly contributes to the formation of deletions and translocations in G1, which represent important initiating events in carcinogenesis.

Typ des Eintrags: Artikel
Erschienen: 2021
Autor(en): Biehs, Ronja ; Steinlage, Monika ; Barton, Olivia ; Juhász, Szilvia ; Künzel, Julia ; Spies, Julian ; Shibata, Atsushi ; Jeggo, Penny A. ; Löbrich, Markus
Art des Eintrags: Zweitveröffentlichung
Titel: DNA Double-Strand Break Resection Occurs during Non-homologous End Joining in G1 but Is Distinct from Resection during Homologous Recombination
Sprache: Englisch
Publikationsjahr: 2021
Publikationsdatum der Erstveröffentlichung: 2017
Verlag: Elsevier
Titel der Zeitschrift, Zeitung oder Schriftenreihe: Molecular Cell
Jahrgang/Volume einer Zeitschrift: 65
(Heft-)Nummer: 4
DOI: 10.26083/tuprints-00013323
URL / URN: https://tuprints.ulb.tu-darmstadt.de/13323
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Herkunft: Zweitveröffentlichungsservice
Kurzbeschreibung (Abstract):

Canonical non-homologous end joining (c-NHEJ) repairs DNA double-strand breaks (DSBs) in G1 cells with biphasic kinetics. We show that DSBs repaired with slow kinetics, including those localizing to heterochromatic regions or harboring additional lesions at the DSB site, undergo resection prior to repair by c-NHEJ and not alt-NHEJ. Resection-dependent c-NHEJ represents an inducible process during which Plk3 phosphorylates CtIP, mediating its interaction with Brca1 and promoting the initiation of resection. Mre11 exonuclease, EXD2, and Exo1 execute resection, and Artemis endonuclease functions to complete the process. If resection does not commence, then repair can ensue by c-NHEJ, but when executed, Artemis is essential to complete resection-dependent c-NHEJ. Additionally, Mre11 endonuclease activity is dispensable for resection in G1. Thus, resection in G1 differs from the process in G2 that leads to homologous recombination. Resection-dependent c-NHEJ significantly contributes to the formation of deletions and translocations in G1, which represent important initiating events in carcinogenesis.

Status: Verlagsversion
URN: urn:nbn:de:tuda-tuprints-133233
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: 13 Aug 2021 12:53
Letzte Änderung: 17 Aug 2021 06:26
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