FANCM interacts with PCNA to promote replication traverse of DNA interstrand crosslinks
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- FANCM is a highly conserved DNA remodeling enzyme that promotes the activation of the Fanconi anemia DNA repair pathway and facilitates replication traverse of DNA interstrand crosslinks. However, how FANCM interacts with the replication machinery to promote traverse remains unclear. Here, we show that FANCM and its archaeal homolog Hef from Thermoplasma acidophilum interact with proliferating cell nuclear antigen (PCNA), an essential co-factor for DNA polymerases in both replication and repair. The interaction is mediated through a conservedFANCM is a highly conserved DNA remodeling enzyme that promotes the activation of the Fanconi anemia DNA repair pathway and facilitates replication traverse of DNA interstrand crosslinks. However, how FANCM interacts with the replication machinery to promote traverse remains unclear. Here, we show that FANCM and its archaeal homolog Hef from Thermoplasma acidophilum interact with proliferating cell nuclear antigen (PCNA), an essential co-factor for DNA polymerases in both replication and repair. The interaction is mediated through a conserved PIP-box; and in human FANCM, it is strongly stimulated by replication stress. A FANCM variant carrying a mutation in the PIP-box is defective in promoting replication traverse of interstrand crosslinks and is also inefficient in promoting FANCD2 monoubiquitination, a key step of the Fanconi anemia pathway. Our data reveal a conserved interaction mode between FANCM and PCNA during replication stress, and suggest that this interaction is essential for FANCM to aid replication machines to traverse DNA interstrand crosslinks prior to post-replication repair.…
Autor(en): | Florian Rohleder, Jing Huang, Yutong Xue, Jochen Kuper, Adam Round, Michael Seidman, Weidong Wang, Caroline Kisker |
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URN: | urn:nbn:de:bvb:20-opus-175401 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Fakultät für Biologie / Rudolf-Virchow-Zentrum |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Nucleic Acids Research |
Erscheinungsjahr: | 2016 |
Band / Jahrgang: | 44 |
Heft / Ausgabe: | 7 |
Seitenangabe: | 3219–3232 |
Originalveröffentlichung / Quelle: | Nucleic Acids Research, 2016, Vol. 44, No. 7, 3219–3232. DOI: 10.1093/nar/gkw037 |
DOI: | https://doi.org/10.1093/nar/gkw037 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 611 Menschliche Anatomie, Zytologie, Histologie |
Freie Schlagwort(e): | FANCM; genome integrity; proliferating cell nuclear antigen (PCNA); repair and replication |
Datum der Freischaltung: | 10.12.2020 |
Lizenz (Deutsch): | CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International |