A conserved Ctp1/CtIP C-terminal peptide stimulates Mre11 endonuclease activity
The Mre11-Rad50-Nbs1 complex (MRN) is important for repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). The endonuclease activity of MRN is critical for resecting 5'-ended DNA strands at DSB ends, producing 3'-ended single-strand DNA, a prerequisite for HR. This endonuclease activity is stimulated by Ctp1, the Schizosaccharomyces pombe homolog of human CtIP. Here, with purified proteins, we show that Ctp1 phosphorylation stimulates MRN endonuclease activity by inducing the association of Ctp1 with Nbs1. The highly conserved extreme C terminus of Ctp1 is indispensable for MRN activation. Importantly, a polypeptide composed of the conserved 15 amino acids at the C terminus of Ctp1 (CT15) is sufficient to stimulate Mre11 endonuclease activity. Furthermore, the CT15 equivalent from CtIP can stimulate human MRE11 endonuclease activity, arguing for the generality of this stimulatory mechanism. Thus, we propose that Nbs1-mediated recruitment of CT15 plays a pivotal role in the activation of the Mre11 endonuclease by Ctp1/CtIP.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:118 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 118(2021), 11 vom: 16. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zdravković, Aleksandar [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.09.2021 Date Revised 23.09.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2016287118 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM323916775 |
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| 041 | |a eng | ||
| 100 | 1 | |a Zdravković, Aleksandar |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A conserved Ctp1/CtIP C-terminal peptide stimulates Mre11 endonuclease activity |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 23.09.2021 | ||
| 500 | |a Date Revised 23.09.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The Mre11-Rad50-Nbs1 complex (MRN) is important for repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). The endonuclease activity of MRN is critical for resecting 5'-ended DNA strands at DSB ends, producing 3'-ended single-strand DNA, a prerequisite for HR. This endonuclease activity is stimulated by Ctp1, the Schizosaccharomyces pombe homolog of human CtIP. Here, with purified proteins, we show that Ctp1 phosphorylation stimulates MRN endonuclease activity by inducing the association of Ctp1 with Nbs1. The highly conserved extreme C terminus of Ctp1 is indispensable for MRN activation. Importantly, a polypeptide composed of the conserved 15 amino acids at the C terminus of Ctp1 (CT15) is sufficient to stimulate Mre11 endonuclease activity. Furthermore, the CT15 equivalent from CtIP can stimulate human MRE11 endonuclease activity, arguing for the generality of this stimulatory mechanism. Thus, we propose that Nbs1-mediated recruitment of CT15 plays a pivotal role in the activation of the Mre11 endonuclease by Ctp1/CtIP | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Ctp1/CtIP | |
| 650 | 4 | |a Mre11-Rad50-Nbs1 | |
| 650 | 4 | |a double-strand break repair | |
| 650 | 4 | |a fission yeast | |
| 650 | 4 | |a homologous recombination | |
| 650 | 7 | |a Ctp1 protein, S pombe |2 NLM | |
| 650 | 7 | |a DNA-Binding Proteins |2 NLM | |
| 650 | 7 | |a Peptides |2 NLM | |
| 650 | 7 | |a Schizosaccharomyces pombe Proteins |2 NLM | |
| 650 | 7 | |a Casein Kinase II |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Exodeoxyribonucleases |2 NLM | |
| 650 | 7 | |a EC 3.1.- |2 NLM | |
| 650 | 7 | |a Mre11 protein, S pombe |2 NLM | |
| 650 | 7 | |a EC 3.1.- |2 NLM | |
| 700 | 1 | |a Daley, James M |e verfasserin |4 aut | |
| 700 | 1 | |a Dutta, Arijit |e verfasserin |4 aut | |
| 700 | 1 | |a Niwa, Tatsuya |e verfasserin |4 aut | |
| 700 | 1 | |a Murayama, Yasuto |e verfasserin |4 aut | |
| 700 | 1 | |a Kanamaru, Shuji |e verfasserin |4 aut | |
| 700 | 1 | |a Ito, Kentaro |e verfasserin |4 aut | |
| 700 | 1 | |a Maki, Takahisa |e verfasserin |4 aut | |
| 700 | 1 | |a Argunhan, Bilge |e verfasserin |4 aut | |
| 700 | 1 | |a Takahashi, Masayuki |e verfasserin |4 aut | |
| 700 | 1 | |a Tsubouchi, Hideo |e verfasserin |4 aut | |
| 700 | 1 | |a Sung, Patrick |e verfasserin |4 aut | |
| 700 | 1 | |a Iwasaki, Hiroshi |e verfasserin |4 aut | |
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| 856 | 4 | 0 | |u http://dx.doi.org/10.1073/pnas.2016287118 |3 Volltext |
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