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CtIP and MRN promote non-homologous end-joining of etoposide-induced DNA double-strand breaks in G1

Quennet, Verena ; Beucher, Andrea ; Barton, Olivia ; Takeda, Shunichi ; Löbrich, Markus (2022):
CtIP and MRN promote non-homologous end-joining of etoposide-induced DNA double-strand breaks in G1. (Publisher's Version)
In: Nucleic Acids Research, 39 (6), pp. 2144-2152. Oxford University Press, ISSN 0305-1048, e-ISSN 1362-4962,
DOI: 10.26083/tuprints-00019509,
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Item Type: Article
Origin: Secondary publication service
Status: Publisher's Version
Title: CtIP and MRN promote non-homologous end-joining of etoposide-induced DNA double-strand breaks in G1
Language: English
Abstract:

Topoisomerases class II (topoII) cleave and re-ligate the DNA double helix to allow the passage of an intact DNA strand through it. Chemotherapeutic drugs such as etoposide target topoII, interfere with the normal enzymatic cleavage/re-ligation reaction and create a DNA double-strand break (DSB) with the enzyme covalently bound to the 5′-end of the DNA. Such DSBs are repaired by one of the two major DSB repair pathways, non-homologous end-joining (NHEJ) or homologous recombination. However, prior to repair, the covalently bound topoII needs to be removed from the DNA end, a process requiring the MRX complex and ctp1 in fission yeast. CtIP, the mammalian ortholog of ctp1, is known to promote homologous recombination by resecting DSB ends. Here, we show that human cells arrested in G0/G1 repair etoposide-induced DSBs by NHEJ and, surprisingly, require the MRN complex (the ortholog of MRX) and CtIP. CtIP's function for repairing etoposide-induced DSBs by NHEJ in G0/G1 requires the Thr-847 but not the Ser-327 phosphorylation site, both of which are needed for resection during HR. This finding establishes that CtIP promotes NHEJ of etoposide-induced DSBs during G0/G1 phase with an end-processing function that is distinct to its resection function.

Journal or Publication Title: Nucleic Acids Research
Volume of the journal: 39
Issue Number: 6
Publisher: Oxford University Press
Classification DDC: 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
Divisions: 10 Department of Biology > Radiation Biology and DNA Repair
Date Deposited: 23 Mar 2022 12:43
Last Modified: 23 Mar 2022 12:43
DOI: 10.26083/tuprints-00019509
Corresponding Links:
URN: urn:nbn:de:tuda-tuprints-195092
Additional Information:

Supplementary Data: https://t1p.de/9wq9q

URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/19509
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