FANCD2
GeneName
FANCD2
Summary
FANCD2, also known as FAD or FACD, is a 164 kDa protein that plays a crucial role in the DNA damage response and repair pathways. It is primarily localised in the nucleus, where it associates with chromatin and forms part of DNA repair complexes. FANCD2 is essential for interstrand cross-link repair and is involved in the repair of double-strand breaks, particularly during meiosis. Additionally, it contributes to brain morphogenesis and the maintenance of neuronal stem cell populations, highlighting its significance in both developmental and cellular stress responses.
Importance
FANCD2 is relevant to: - DNA repair mechanisms, especially in the context of interstrand cross-links and double-strand breaks, which are critical for genomic stability - Cellular responses to oxidative stress, influencing the survival and function of cells under stress conditions - Gamete generation and meiotic processes, impacting fertility and developmental biology - Regulation of immune responses, particularly in T cell differentiation and inflammatory pathways, which may have implications for autoimmune diseases and cancer
Top Products
For researchers investigating FANCD2, we highly recommend the top-selling recombinant antibody, Anti-FANCD2 antibody [EPR2302] (ab108928). This well-cited antibody has garnered 58 citations, reflecting its strong reputation in the field. It has been validated in knockout models and is suitable for a variety of applications, including Western blotting (WB), immunocytochemistry (ICC), immunohistochemistry (IHC), immunoprecipitation (IP), and flow cytometry (FC). This versatility makes it an excellent choice for those seeking reliable detection of FANCD2 across different experimental setups.
Abcam Product Citation Summary
The use of Abcam antibody ab108928 for FANCD2 detection highlights its relevance in various biological contexts involving mouse models. The studies focus on critical processes such as p53 activation, meiosis, Fanconi anemia, and bone marrow hematopoiesis, indicating the importance of FANCD2 in genomic stability and cellular functions.
Abcam Product Citation Table
Developmental stage
Highly expressed in fetal oocytes, and in hematopoietic cells of the fetal liver and bone marrow (at protein level).
Domain
The C-terminal 24 residues of isoform 2 are required for its function.
Function
Required for maintenance of chromosomal stability. Promotes accurate and efficient pairing of homologs during meiosis. Involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing. May participate in S phase and G2 phase checkpoint activation upon DNA damage. Plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress. Required for the targeting, or stabilization, of BLM to non-centromeric abnormal structures induced by replicative stress. Promotes BRCA2/FANCD1 loading onto damaged chromatin. May also be involved in B-cell immunoglobulin isotype switching.
Involvement in disease
Fanconi anemia complementation group D2
FANCD2
A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Monoubiquitinated on Lys-561 during S phase and upon genotoxic stress by FANCL in complex with E2 ligases UBE2T or UBE2W (isoform 1 and isoform 2). Deubiquitinated by USP1 as cells enter G2/M, or once DNA repair is completed. Monoubiquitination requires the joint intervention of the FANC core complex, including FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, and FANCM, and proteins involved in cell cycle checkpoints and DNA repair, including RPA1, ATR, CHEK1 and BRCA1, and is mediated by FANCL/PHF9. Ubiquitination is required for binding to chromatin, interaction with BRCA1, BRCA2 and MTMR15/FAN1, DNA repair, and normal cell cycle progression, but not for phosphorylation on Ser-222 or interaction with MEN1.
Phosphorylated in response to various genotoxic stresses by ATM and/or ATR. Upon ionizing radiation, phosphorylated by ATM on Ser-222 and Ser-1404. Phosphorylation on Ser-222 is required for S-phase checkpoint activation, but not for ubiquitination, foci formation, or DNA repair. In contrast, phosphorylation by ATR on other sites may be required for ubiquitination and foci formation.
Tissue Specificity
Highly expressed in germinal center cells of the spleen, tonsil, and reactive lymph nodes, and in the proliferating basal layer of squamous epithelium of tonsil, esophagus, oropharynx, larynx and cervix. Expressed in cytotrophoblastic cells of the placenta and exocrine cells of the pancreas (at protein level). Highly expressed in testis, where expression is restricted to maturing spermatocytes.
Cellular localization
- Nucleus
- Concentrates in nuclear foci during S phase and upon genotoxic stress. At the onset of mitosis, excluded from chromosomes and diffuses into the cytoplasm, returning to the nucleus at the end of cell division. Observed in a few spots localized in pairs on the sister chromatids of mitotic chromosome arms and not centromeres, one on each chromatids. These foci coincide with common fragile sites and could be sites of replication fork stalling. The foci are frequently interlinked through BLM-associated ultra-fine DNA bridges. Following aphidicolin treatment, targets chromatid gaps and breaks.
Alternative names
FACD, FANCD2, Fanconi anemia group D2 protein, Protein FACD2
Database links
swissprot:Q9BXW9 omim:613984 entrezGene:2177
Other research areas
- Epigenetics