FANCD2 binds CtIP and regulates DNA-end resection during DNA interstrand crosslink repair.

The Fanconi anemia (FA) pathway is critically involved in the maintenance of hematopoietic stem cells and the suppression of carcinogenesis. A key FA protein, FANCD2, is monoubiquitinated and accumulates in chromatin in response to DNA interstrand crosslinks (ICLs), where it coordinates DNA repair through mechanisms that are still poorly understood. Here, we report that CtIP protein directly interacts with FANCD2. A region spanning amino acids 166 to 273 of CtIP and monoubiquitination of FANCD2 are both essential for the FANCD2-CtIP interaction and mitomycin C (MMC)-induced CtIP foci. Remarkably, both FANCD2 and CtIP are critical for MMC-induced RPA2 hyperphosphorylation, an event that accompanies end resection of double-strand breaks. Collectively, our results reveal a role of monoubiquitinated FANCD2 in end resection that depends on its binding to CtIP during ICL repair.

• Publication year

  2014

• Venue

  Cell Reports

• Publication date

  2014-05-22

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.celrep.2014.04.005PMID 24794430
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• FANCD2 and CtIP cooperate to repair DNA interstrand crosslinks.

  2014cited by this paper
• Fanconi anaemia and the repair of Watson and Crick DNA crosslinks

  2013influential reference
• Mutations in ERCC4, encoding the DNA-repair endonuclease XPF, cause Fanconi anemia.

  2013cited by this paper
• Recognition, signaling, and repair of DNA double-strand breaks produced by ionizing radiation in mammalian cells: the molecular choreography.

  2012cited by this paper
• CtIP Protein Dimerization Is Critical for Its Recruitment to Chromosomal DNA Double-stranded Breaks*

  2012cited by this paper
• CtIP Is Required to Initiate Replication-Dependent Interstrand Crosslink Repair

  2012cited by this paper
• DNA robustly stimulates FANCD2 monoubiquitylation in the complex with FANCI

  2012cited by this paper
• Playing the end game: DNA double-strand break repair pathway choice.

  2012cited by this paper
• FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair

  2012cited by this paper
• BRCA1 functions independently of homologous recombination in DNA interstrand crosslink repair.

  2012cited by this paper
• DNA2 and EXO1 in replication-coupled, homology-directed repair and in the interplay between HDR and the FA/BRCA network

  2012cited by this paper
• Histone chaperone activity of Fanconi anemia proteins, FANCD2 and FANCI, is required for DNA crosslink repair

  2012cited by this paper
• Involvement of SLX4 in interstrand cross-link repair is regulated by the Fanconi anemia pathway

  2012cited by this paper
• Regulation of DNA cross-link repair by the Fanconi anemia/BRCA pathway.

  2012influential reference
• SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtype

  2011cited by this paper
• Involvement of SLX4 in interstrand cross-link repair is regulated by the Fanconi anemia pathway

  2011cited by this paper
• Mutations of the SLX4 gene in Fanconi anemia

  2011influential reference
• Double-strand break end resection and repair pathway choice.

  2011cited by this paper
• DNA resection in eukaryotes: deciding how to fix the break

  2010influential reference
• KIAA1018/FAN1 nuclease protects cells against genomic instability induced by interstrand cross-linking agents

  2010cited by this paper
• Fanconi anemia and its diagnosis.

  2009cited by this paper
• Ubiquitin-binding domains and their role in the DNA damage response.

  2009cited by this paper
• CtIP links DNA double-strand break sensing to resection.

  2009cited by this paper
• DNA double-strand break processing: the beginning of the end.

  2008cited by this paper
• Cell cycle-dependent chromatin loading of the Fanconi anemia core complex by FANCM/FAAP24.

  2008influential reference
• Human CtIP promotes DNA end resection

  2007influential reference
• BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP.

  2006cited by this paper
• Direct observation of individual endogenous protein complexes in situ by proximity ligation

  2006cited by this paper
• Dimerization of CtIP, a BRCA1- and CtBP-interacting Protein, Is Mediated by an N-terminal Coiled-coil Motif*

  2004cited by this paper
• BRCA1-independent ubiquitination of FANCD2.

  2003cited by this paper
• FANCE: the link between Fanconi anaemia complex assembly and activity

  2002cited by this paper
• Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis.

  2000influential reference
• Interaction between a Cellular Protein That Binds to the C-terminal Region of Adenovirus E1A (CtBP) and a Novel Cellular Protein Is Disrupted by E1A through a Conserved PLDLS Motif*

  1998cited by this paper

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• Mechanisms and regulation of DNA end resection in the maintenance of genome stability

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  2024cites this paper
• FANCD2 counteracts O6-methylguanine-induced mismatch repair-dependent apoptosis

  2024cites this paper
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  2023cites this paper
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  2022cites this paper
• CHAMP1-POGZ counteracts the inhibitory effect of 53BP1 on homologous recombination and affects PARP inhibitor resistance

  2022influential citation
• NEIL3 contributes to the Fanconi anemia/BRCA pathway by promoting the downstream double-strand break repair step.

  2022cites this paper
• Fanconi anemia: current insights regarding epidemiology, cancer, and DNA repair

  2022cites this paper
• FANCD2 and RAD51 recombinase directly inhibit DNA2 nuclease at stalled replication forks and FANCD2 acts as a novel RAD51 mediator in strand exchange to promote genome stability

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  2021cites this paper
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  2021cites this paper
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  2021cites this paper
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  2020cites this paper
• Cooperation of the ATM and Fanconi Anemia/BRCA Pathways in Double-Strand Break End Resection.

  2020cites this paper
• DNA double-strand break end resection: a critical relay point for determining the pathway of repair and signaling

  2020cites this paper
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  2020cites this paper
• Holding All the Cards—How Fanconi Anemia Proteins Deal with Replication Stress and Preserve Genomic Stability

  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
• TRIM66 reads unmodified H3R2K4 and H3K56ac to respond to DNA damage in embryonic stem cells

  2019cites this paper
• The Fanconi Anemia Pathway in Cancer.

  2019cites this paper
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  2018cites this paper
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  2018cites this paper
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• Mechanisms for stalled replication fork stabilization: new targets for synthetic lethality strategies in cancer treatments

  2018cites this paper
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  2018cites this paper
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  2018cites this paper
• Biochemical Characterization of FAN1 Nuclease

  2018cites this paper
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  2017cites this paper
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  2017cites this paper
• The emerging role of RNAs in DNA damage repair

  2017cites this paper
• Reduced recruitment of 53BP1 during interstrand crosslink repair is associated with genetically inherited attenuation of mitomycin C sensitivity in a family with Fanconi anemia

  2017influential citation
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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• Repair Pathway Choices and Consequences at the Double-Strand Break.

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  2016cites this paper
• Cellular response to DNA interstrand crosslinks: the Fanconi anemia pathway

  2016cites this paper
• The Fanconi anaemia pathway: new players and new functions

  2016cites this paper
• Defects in homologous recombination repair behind the human diseases: FA and HBOC.

  2016cites this paper
• Mutations in the gene encoding the E2 conjugating enzyme UBE2T cause Fanconi anemia.

  2015cites this paper
• Association of human papillomavirus with Fanconi anemia promotes carcinogenesis in Fanconi anemia patients

  2015cites this paper
• When two is not enough: a CtIP tetramer is required for DNA repair by Homologous Recombination

  2015cites this paper
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• Fanconi anaemia: genetics, molecular biology, and cancer – implications for clinical management in children and adults

  2015cites this paper
• Human FAN1 promotes strand incision in 5'-flapped DNA complexed with RPA.

  2015cites this paper
• Promoting Genome Stability via Multiple DNA Repair Pathways

  2015cites this paper
• The role of the Fanconi anemia pathway in sporadic head and neck cancer

  2015cites this paper
• CtIP: A DNA damage response protein at the intersection of DNA metabolism.

  2015cites this paper
• FANCD2 influences replication fork processes and genome stability in response to clustered DSBs

  2015cites this paper
• What is the DNA repair defect underlying Fanconi anemia?

  2015influential citation
• Exploiting replicative stress to treat cancer

  2015cites this paper
• The Fanconi Anemia Pathway of DNA Repair and Human Cancer

  2015cites this paper
• Role of Deubiquitinating Enzymes in DNA Repair

  2015cites this paper
• Genetic Diagnosis of Fanconi Anemia

  2015cites this paper
• Defective FANCI Binding by a Fanconi Anemia-Related FANCD2 Mutant

  2014cites this paper
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• Genotoxicity of formaldehyde: molecular basis of DNA damage and mutation

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