Fanconi anemia-associated mutation in RAD51 compromises the coordinated action of DNA-binding and ATPase activities

Liu, Sijia; Shinohara, Akira; Furukohri, Asako

doi:https://doi.org/10.1016/j.jbc.2023.105424

Fanconi anemia-associated mutation in RAD51 compromises the coordinated action of DNA-binding and ATPase activities

Liu, Sijia; Shinohara, Akira; Furukohri, Asako

Journal of Biological Chemistry, 2023, 299(12), 105424

Number of Access:369（2025-08-15 06:46 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93374

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Title	Fanconi anemia-associated mutation in RAD51 compromises the coordinated action of DNA-binding and ATPase activities
Creator	CreatorName Liu, Sijia
	NRID 1000000252578 1000000252578 ORCID 0000-0003-4207-8247 0000-0003-4207-8247 researchmap permalink akirashinohara13 akirashinohara13 Scopus Author ID 7102342573 7102342573 CreatorName Shinohara, Akira
	NRID 1000090546293 1000090546293 researchmap permalink afurukohri afurukohri Scopus Author ID 25228605000 25228605000 CreatorName Furukohri, Asako
Subject	DNA binding protein
	DNA repair
	Fanconi anemia
	homologous recombination
	RAD51
Description	Liu S., Shinohara A., Furukohri A.. Fanconi anemia-associated mutation in RAD51 compromises the coordinated action of DNA-binding and ATPase activities. Journal of Biological Chemistry 299, 105424 (2023); https://doi.org/10.1016/j.jbc.2023.105424.
Abstract	Fanconi anemia (FA) is a rare genetic disease caused by a defect in DNA repair pathway for DNA interstrand crosslinks. These crosslinks can potentially impede the progression of the DNA replication fork, consequently leading to DNA double-strand breaks. Heterozygous RAD51-Q242R mutation has been reported to cause FA-like symptoms. However, the molecular defect of RAD51 underlying the disease is largely unknown. In this study, we conducted a biochemical analysis of RAD51-Q242R protein, revealing notable deficiencies in its DNA-dependent ATPase activity and its ATP-dependent regulation of DNA-binding activity. Interestingly, although RAD51-Q242R exhibited the filament instability and lacked the ability to form displacement loop, it efficiently stimulated the formation of displacement loops mediated by wild-type RAD51. These findings facilitate understanding of the biochemical properties of the mutant protein and how RAD51 works in the FA patient cells.
Publisher	American Society for Biochemistry and Molecular Biology Inc.
Source Title	Journal of Biological Chemistry
Volume (Issue)	299(12)
Page	105424
Date of Issued	2023-12-01
Language	English
Handle URL	https://hdl.handle.net/11094/93374
PISSN	00219258
eISSN	1083351X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1016/j.jbc.2023.105424
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Journal of Biological Chemistry. 2023, 299(12), p. 105424
DC.title	Fanconi anemia-associated mutation in RAD51 compromises the coordinated action of DNA-binding and ATPase activities
DC.creator	Liu, Sijia
	Shinohara, Akira
	Furukohri, Asako
DC.publisher	American Society for Biochemistry and Molecular Biology Inc.
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2023-12-01
DC.identifier	https://doi.org/10.1016/j.jbc.2023.105424
DC.subject	DNA binding protein
	DNA repair
	Fanconi anemia
	homologous recombination
	RAD51
DC.description	Liu S., Shinohara A., Furukohri A.. Fanconi anemia-associated mutation in RAD51 compromises the coordinated action of DNA-binding and ATPase activities. Journal of Biological Chemistry 299, 105424 (2023); https://doi.org/10.1016/j.jbc.2023.105424.
DCTERMS.abstract	Fanconi anemia (FA) is a rare genetic disease caused by a defect in DNA repair pathway for DNA interstrand crosslinks. These crosslinks can potentially impede the progression of the DNA replication fork, consequently leading to DNA double-strand breaks. Heterozygous RAD51-Q242R mutation has been reported to cause FA-like symptoms. However, the molecular defect of RAD51 underlying the disease is largely unknown. In this study, we conducted a biochemical analysis of RAD51-Q242R protein, revealing notable deficiencies in its DNA-dependent ATPase activity and its ATP-dependent regulation of DNA-binding activity. Interestingly, although RAD51-Q242R exhibited the filament instability and lacked the ability to form displacement loop, it efficiently stimulated the formation of displacement loops mediated by wild-type RAD51. These findings facilitate understanding of the biochemical properties of the mutant protein and how RAD51 works in the FA patient cells.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	93374
citation_title	Fanconi anemia-associated mutation in RAD51 compromises the coordinated action of DNA-binding and ATPase activities
citation_author	Liu, Sijia
	Shinohara, Akira
	Furukohri, Asako
citation_publisher	American Society for Biochemistry and Molecular Biology Inc.
citation_language	English
citation_date	2023-12-01
citation_journal_title	Journal of Biological Chemistry
citation_volume	299
citation_issue	12
citation_firstpage	105424
citation_doi	https://doi.org/10.1016/j.jbc.2023.105424
citation_public_url	https://hdl.handle.net/11094/93374

Fanconi anemia-associated mutation in RAD51 compromises the coordinated action of DNA-binding and ATPase activities

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