ArticleNucleic acids research2017
The identification of FANCD2 DNA binding domains reveals nuclear localization sequences.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Clinical relevance of double heterozygosity revealed by next-generation sequencing of homologous recombination repair pathway genes in South African breast cancer patients.Breast cancer research and treatment · 2024Article
- 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.Nucleic acids research · 2023Article
- Multiple cancers escape from multiple MAPK pathway inhibitors and use DNA replication stress signaling to tolerate aberrant cell cycles.Science signaling · 2023Article
- Fanconi anemia: current insights regarding epidemiology, cancer, and DNA repair.Human genetics · 2022Review
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- Making Connections: Integrative Signaling Mechanisms Coordinate DNA Break Repair in Chromatin.Frontiers in genetics · 2021Review
- Article
- Subcellular localization of FANCD2 is associated with survival in ovarian carcinoma.Oncotarget · 2020Article
- A Fanci knockout mouse model reveals common and distinct functions for FANCI and FANCD2.Nucleic acids research · 2019Article
- FANCD2 Binding to H4K20me2 via a Methyl-Binding Domain Is Essential for Efficient DNA Cross-Link Repair.Molecular and cellular biology · 2019Article
- Poly(ADP-ribose) polymerase-1 antagonizes DNA resection at double-strand breaks.Nature communications · 2019Article
- Phosphorylation of FANCD2 Inhibits the FANCD2/FANCI Complex and Suppresses the Fanconi Anemia Pathway in the Absence of DNA Damage.Cell reports · 2019Article
- The Fanconi Anemia Pathway in Cancer.Annual review of cancer biology · 2019Article
- Lymphopenia With Clinical and Laboratory Features of Combined Immune Deficiency in an 11-Year-Old Female WithFrontiers in pediatrics · 2018Article
- FANCI and FANCD2 have common as well as independent functions during the cellular replication stress response.Nucleic acids research · 2017Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fanconi anemia (FA) is a recessive genetic disorder characterized by congenital abnormalities, progressive bone-marrow failure, and cancer susceptibility. The FA pathway consists of at least 21 FANC genes (FANCA-FANCV), and the encoded protein products interact in a common cellular pathway to gain resistance against DNA interstrand crosslinks. After DNA damage, FANCD2 is monoubiquitinated and accumulates on chromatin. FANCD2 plays a central role in the FA pathway, using yet unidentified DNA binding regions. By using synthetic peptide mapping and DNA binding screen by electromobility shift assays, we found that FANCD2 bears two major DNA binding domains predominantly consisting of evolutionary conserved lysine residues. Furthermore, one domain at the N-terminus of FANCD2 bears also nuclear localization sequences for the protein. Mutations in the bifunctional DNA binding/NLS domain lead to a reduction in FANCD2 monoubiquitination and increase in mitomycin C sensitivity. Such phenotypes are not fully rescued by fusion with an heterologous NLS, which enable separation of DNA binding and nuclear import functions within this domain that are necessary for FANCD2 functions. Collectively, our results enlighten the importance of DNA binding and NLS residues in FANCD2 to activate an efficient FA pathway.
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