Fanconi anemia proteins participate in a break-induced-replication-like pathway to counter replication stress.

Aneuploidy Animals Bone Marrow Failure Disorders / etiology Cell Line, Transformed Chickens Chromosome Breakage Chromosome Deletion Chromosomes, Human, Pair 7 / genetics DNA Polymerase III / physiology DNA Replication / genetics Disease Progression Fanconi Anemia / genetics Fanconi Anemia Complementation Group Proteins / deficiency Female HCT116 Cells HEK293 Cells Humans Hydroxyurea / pharmacology Leukemia, Myeloid, Acute / genetics Male Mice Mice, Inbred C57BL Mice, Knockout Models, Genetic Species Specificity Tumor Suppressor p53-Binding Protein 1 / physiology Ubiquitin-Protein Ligases / physiology

Journal

Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374

Informations de publication

Date de publication:
06 2021
Historique:
received: 19 08 2020
accepted: 30 04 2021
entrez: 12 6 2021
pubmed: 13 6 2021
medline: 25 8 2021
Statut: ppublish

Résumé

Fanconi anemia (FA) is a devastating hereditary disease characterized by bone marrow failure (BMF) and acute myeloid leukemia (AML). As FA-deficient cells are hypersensitive to DNA interstrand crosslinks (ICLs), ICLs are widely assumed to be the lesions responsible for FA symptoms. Here, we show that FA-mutated cells are hypersensitive to persistent replication stress and that FA proteins play a role in the break-induced-replication (BIR)-like pathway for fork restart. Both the BIR-like pathway and ICL repair share almost identical molecular mechanisms of 53BP1-BRCA1-controlled signaling response, SLX4- and FAN1-mediated fork cleavage and POLD3-dependent DNA synthesis, suggesting that the FA pathway is intrinsically one of the BIR-like pathways. Replication stress not only triggers BMF in FA-deficient mice, but also specifically induces monosomy 7, which is associated with progression to AML in patients with FA, in FA-deficient cells.

Identifiants

DOI: 10.1038/s41594-021-00602-9 PMID: 34117478
pubmed: 34117478
doi: 10.1038/s41594-021-00602-9
pii: 10.1038/s41594-021-00602-9
doi:

Substances chimiques

Fanconi Anemia Complementation Group Proteins 0
TP53BP1 protein, human 0
Tumor Suppressor p53-Binding Protein 1 0
BRAP protein, human EC 2.3.2.27
Ubiquitin-Protein Ligases EC 2.3.2.27
POLD3 protein, human EC 2.7.7.-
DNA Polymerase III EC 2.7.7.7
Hydroxyurea X6Q56QN5QC

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

487-500

Références

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Auteurs

Xinlin Xu (X)

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.

Yixi Xu (Y)

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China. xuyixi@westlake.edu.cn.
School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China. xuyixi@westlake.edu.cn.
ORCID: 0000-0003-4139-7772

Ruiyuan Guo (R)

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.

Ran Xu (R)

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.

Congcong Fu (C)

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.

Mengtan Xing (M)

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.
Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Science and Technology, Shanghai Key Laboratory of Signaling and Disease Research, Tongji University, Shanghai, China.

Hiroyuki Sasanuma (H)

Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Qing Li (Q)

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.
ORCID: 0000-0003-0251-9159

Minoru Takata (M)

Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.

Shunichi Takeda (S)

Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
ORCID: 0000-0002-7924-7991

Rong Guo (R)

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China. guorong@pku.edu.cn.
ORCID: 0000-0003-3203-614X

Dongyi Xu (D)

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China. xudongyi@pku.edu.cn.
ORCID: 0000-0001-5711-2618

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Ploïdies › Aneuploïdie › Fanconi anemia proteins participate in a...
questionsmedicales.fr › Eucaryotes › Animaux › Fanconi anemia proteins participate in a...
questionsmedicales.fr › Hémopathies et maladies lymphatiques › Hémopathies › Maladies de la moelle osseuse › Aplasies médullaires › Fanconi anemia proteins participate in a...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › Lignée de cellules transformées › Fanconi anemia proteins participate in a...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Oiseaux › Poulets › Fanconi anemia proteins participate in a...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Aberrations des chromosomes › Cassure de chromosome › Fanconi anemia proteins participate in a...
questionsmedicales.fr › Phénomènes génétiques › Ploïdies › Aneuploïdie › Monosomie › Délétion de segment de chromosome › Fanconi anemia proteins participate in a...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Chromosomes › Chromosomes de mammifère › Chromosomes humains › Chromosomes humains 6-12 et X › Chromosomes humains de la paire 7 › Fanconi anemia proteins participate in a...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Nucleotidyltransferases › DNA nucleotidyltransferases › DNA-directed DNA polymerase › DNA polymerase III › Fanconi anemia proteins participate in a...
questionsmedicales.fr › Phénomènes génétiques › Réplication de l'ADN › Fanconi anemia proteins participate in a...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Fanconi anemia proteins participate in a...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Troubles dus à un défaut de réparation de l'ADN › Anémie de Fanconi › Fanconi anemia proteins participate in a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines des groupes de complémentation de l'anémie de Fanconi › Fanconi anemia proteins participate in a...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Cellules HCT116 › Fanconi anemia proteins participate in a...
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questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Leucémies › Leucémie myéloïde › Leucémie aigüe myéloïde › Fanconi anemia proteins participate in a...
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questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Fanconi anemia proteins participate in a...
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questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines chromosomiques nonhistones › Protéine-1 liant le suppresseur de tumeur p53 › Fanconi anemia proteins participate in a...
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