CHAMP1 binds to REV7/FANCV and promotes homologous recombination repair
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved..
A critical determinant of DNA repair pathway choice is REV7, an adaptor that binds to various DNA repair proteins through its C-terminal seatbelt domain. The REV7 seatbelt binds to either REV3, activating translesion synthesis, or to SHLD3, activating non-homologous end joining (NHEJ) repair. Recent studies have identified another REV7 seatbelt-binding protein, CHAMP1 (chromosome alignment-maintaining phosphoprotein 1), though its possible role in DNA repair is unknown. Here, we show that binding of CHAMP1 to REV7 activates homologous recombination (HR) repair. Mechanistically, CHAMP1 binds directly to REV7 and reduces the level of the Shieldin complex, causing an increase in double-strand break end resection. CHAMP1 also interacts with POGZ in a heterochromatin complex further promoting HR repair. Importantly, in human tumors, CHAMP1 overexpression promotes HR, confers poly (ADP-ribose) polymerase inhibitor resistance, and correlates with poor prognosis. Thus, by binding to either SHLD3 or CHAMP1 through its seatbelt, the REV7 protein can promote either NHEJ or HR repair, respectively.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
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| Enthalten in: |
Cell reports - 40(2022), 9 vom: 30. Aug., Seite 111297 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Feng [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.09.2022 Date Revised 18.10.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2022.111297 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a CHAMP1 binds to REV7/FANCV and promotes homologous recombination repair |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a A critical determinant of DNA repair pathway choice is REV7, an adaptor that binds to various DNA repair proteins through its C-terminal seatbelt domain. The REV7 seatbelt binds to either REV3, activating translesion synthesis, or to SHLD3, activating non-homologous end joining (NHEJ) repair. Recent studies have identified another REV7 seatbelt-binding protein, CHAMP1 (chromosome alignment-maintaining phosphoprotein 1), though its possible role in DNA repair is unknown. Here, we show that binding of CHAMP1 to REV7 activates homologous recombination (HR) repair. Mechanistically, CHAMP1 binds directly to REV7 and reduces the level of the Shieldin complex, causing an increase in double-strand break end resection. CHAMP1 also interacts with POGZ in a heterochromatin complex further promoting HR repair. Importantly, in human tumors, CHAMP1 overexpression promotes HR, confers poly (ADP-ribose) polymerase inhibitor resistance, and correlates with poor prognosis. Thus, by binding to either SHLD3 or CHAMP1 through its seatbelt, the REV7 protein can promote either NHEJ or HR repair, respectively | ||
| 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 CHAMP1 | |
| 650 | 4 | |a CP: Molecular biology | |
| 650 | 4 | |a Fanconi anemia | |
| 650 | 4 | |a REV7 | |
| 650 | 4 | |a TRIP13 | |
| 650 | 4 | |a homologous recombination | |
| 650 | 7 | |a CHAMP1 protein, human |2 NLM | |
| 650 | 7 | |a Cell Cycle Proteins |2 NLM | |
| 650 | 7 | |a Chromosomal Proteins, Non-Histone |2 NLM | |
| 650 | 7 | |a MAD2L2 protein, human |2 NLM | |
| 650 | 7 | |a Mad2 Proteins |2 NLM | |
| 650 | 7 | |a Phosphoproteins |2 NLM | |
| 650 | 7 | |a Poly(ADP-ribose) Polymerase Inhibitors |2 NLM | |
| 650 | 7 | |a Transposases |2 NLM | |
| 650 | 7 | |a EC 2.7.7.- |2 NLM | |
| 700 | 1 | |a Sarangi, Prabha |e verfasserin |4 aut | |
| 700 | 1 | |a Iyer, Divya Ramalingam |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Hanrong |e verfasserin |4 aut | |
| 700 | 1 | |a Moreau, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Nguyen, Huy |e verfasserin |4 aut | |
| 700 | 1 | |a Clairmont, Connor |e verfasserin |4 aut | |
| 700 | 1 | |a D'Andrea, Alan D |e verfasserin |4 aut | |
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