ArticleCell reports2023
Phosphorylation by ATR triggers FANCD2 chromatin loading and activates the Fanconi anemia pathway.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- The FANCD2-FANCI heterodimer coordinates chromatin openness and cell cycle progression throughout DNA double-strand break repair.Cell reports · 2026Article
- Loss of UXS1 Selectively Depletes Pyrimidines and Induces Replication Stress in KEAP1-Mutant Lung Cancer.Cancer research · 2025Article
- Comprehensive review on Fanconi anemia: insights into DNA interstrand cross-links, repair pathways, and associated tumors.Orphanet journal of rare diseases · 2025Review
- Knockdown of FANCI suppresses hepatocellular carcinoma development via the PI3K/Akt/GSK-3β pathway.Heliyon · 2025Article
- Ultrarare Variants in DNA Damage Repair Genes in Pediatric Acute-Onset Neuropsychiatric Syndrome or Acute Behavioral Regression in Neurodevelopmental Disorders.Developmental neuroscience · 2025Article
- PP2A licenses the FANCD2/FANCI complex for chromosome loading.Cell reports · 2024Article
- Single-molecule fluorescence imaging of DNA maintenance protein binding dynamics and activities on extended DNA.Current opinion in structural biology · 2024Review
- DoUBLing up: ubiquitin and ubiquitin-like proteases in genome stability.The Biochemical journal · 2024Review
- Piperine Targets the FANCL/UBE2T Complex to Inhibit the FA Pathway and Sensitize Bladder Cancer to Cisplatin.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The Fanconi anemia (FA) pathway repairs DNA interstrand crosslinks (ICLs) in humans. Activation of the pathway relies on loading of the FANCD2/FANCI complex onto chromosomes, where it is fully activated by subsequent monoubiquitination. However, the mechanism for loading the complex onto chromosomes remains unclear. Here, we identify 10 SQ/TQ phosphorylation sites on FANCD2, which are phosphorylated by ATR in response to ICLs. Using a range of biochemical assays complemented with live-cell imaging including super-resolution single-molecule tracking, we show that these phosphorylation events are critical for loading of the complex onto chromosomes and for its subsequent monoubiquitination. We uncover how the phosphorylation events are tightly regulated in cells and that mimicking their constant phosphorylation leads to an uncontrolled active state of FANCD2, which is loaded onto chromosomes in an unrestrained fashion. Taken together, we describe a mechanism where ATR triggers FANCD2/FANCI loading onto chromosomes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.