C57BL/6JCya-Fancd2em1flox/Cya
Common Name:
Fancd2-flox
Product ID:
S-CKO-05592
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
Price:
Contact for Pricing
Basic Information
Strain Name
Fancd2-flox
Strain ID
CKOCMP-211651-Fancd2-B6J-VA
Gene Name
Product ID
S-CKO-05592
Gene Alias
2410150O07Rik; FA-D2; FA4; FACD; FAD; FANCD
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
6
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Fancd2em1flox/Cya mice (Catalog S-CKO-05592) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000036340
NCBI RefSeq
NM_001033244
Target Region
Exon 4~7
Size of Effective Region
~3.4 kb
Detailed Document
Overview of Gene Research
FANCD2, the Fanconi anemia group D2 protein, is a pivotal component of the Fanconi anemia (FA) signaling pathway, a key genomic maintenance pathway. This pathway is activated in response to replication stress, and FANCD2 plays crucial roles in multiple aspects of cellular life, especially in the cellular responses to DNA damage [3].
Phosphorylation of FANCD2 by CHK1 triggers its FBXL12-dependent proteasomal degradation, facilitating its clearance at stalled replication forks and promoting efficient DNA replication under replication stress conditions [1]. Defects in the FA pathway, including those related to FANCD2, lead to R-loop accumulation, which contributes to genomic instability. The splicing factor SRSF1 and FANCD2 interact physically to suppress R-loop formation via mRNA export regulation [2]. Also, FANCD2-dependent mitotic DNA synthesis relies on PCNA K164 ubiquitination, as lack of this ubiquitination impairs FANCD2-dependent functions [4]. FANCD2-FANCI complex surveys DNA, binds to double-stranded DNA and stalls at single-stranded-double-stranded DNA junctions, identifying sites of DNA damage [5]. Monoubiquitination of FANCD2 and FANCI by the FA core complex is a key step in the FA pathway, and deubiquitination by the USP1-UAF1 complex is also critical for interstrand cross-link (ICL) repair [6,7]. In SHH medulloblastoma, FANCD2 is highly expressed, and its deficiency sensitizes the tumor cells to radiotherapy via ferroptosis [8]. A PP2A phosphatase complex dephosphorylates an inhibitory cluster in FANCD2, licensing its loading onto chromosomes in response to DNA damage [9]. In osteosarcoma, FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway [10].
In conclusion, FANCD2 is essential for DNA damage response, replication fork protection, and regulation of processes like R-loop formation, mitotic DNA synthesis, and ferroptosis. Studies related to FANCD2, including those using loss-of-function models, have enhanced our understanding of its role in diseases such as cancer, highlighting its potential as a therapeutic target in certain cancers like SHH medulloblastoma and osteosarcoma.
References：
1. Brunner, Andrä, Li, Qiuzhen, Fisicaro, Samuele, Orre, Lukas M, Sangfelt, Olle. 2023. FBXL12 degrades FANCD2 to regulate replication recovery and promote cancer cell survival under conditions of replication stress. In Molecular cell, 83, 3720-3739.e8. doi:10.1016/j.molcel.2023.07.026. https://pubmed.ncbi.nlm.nih.gov/37591242/
2. Olazabal-Herrero, Anne, He, Boxue, Kwon, Youngho, Sung, Patrick, Kupfer, Gary M. 2024. The FANCI/FANCD2 complex links DNA damage response to R-loop regulation through SRSF1-mediated mRNA export. In Cell reports, 43, 113610. doi:10.1016/j.celrep.2023.113610. https://pubmed.ncbi.nlm.nih.gov/38165804/
3. Nepal, Manoj, Che, Raymond, Ma, Chi, Zhang, Jun, Fei, Peiwen. 2017. FANCD2 and DNA Damage. In International journal of molecular sciences, 18, . doi:10.3390/ijms18081804. https://pubmed.ncbi.nlm.nih.gov/28825622/
4. Leung, Wendy, Baxley, Ryan M, Traband, Emma, Shima, Naoko, Bielinsky, Anja-Katrin. 2023. FANCD2-dependent mitotic DNA synthesis relies on PCNA K164 ubiquitination. In Cell reports, 42, 113523. doi:10.1016/j.celrep.2023.113523. https://pubmed.ncbi.nlm.nih.gov/38060446/
5. Alcón, Pablo, Kaczmarczyk, Artur P, Ray, Korak Kumar, Rueda, David S, Passmore, Lori A. 2024. FANCD2-FANCI surveys DNA and recognizes double- to single-stranded junctions. In Nature, 632, 1165-1173. doi:10.1038/s41586-024-07770-w. https://pubmed.ncbi.nlm.nih.gov/39085614/
6. Li, Landing, Tan, Winnie, Deans, Andrew J. . Structural insight into FANCI-FANCD2 monoubiquitination. In Essays in biochemistry, 64, 807-817. doi:10.1042/EBC20200001. https://pubmed.ncbi.nlm.nih.gov/32725171/
7. Lemonidis, Kimon, Arkinson, Connor, Rennie, Martin L, Walden, Helen. 2021. Mechanism, specificity, and function of FANCD2-FANCI ubiquitination and deubiquitination. In The FEBS journal, 289, 4811-4829. doi:10.1111/febs.16077. https://pubmed.ncbi.nlm.nih.gov/34137174/
8. Zhou, Hong, Wang, Yan-Xia, Wu, Min, Wang, Yan, Bian, Xiu-Wu. 2024. FANCD2 deficiency sensitizes SHH medulloblastoma to radiotherapy via ferroptosis. In The Journal of pathology, 262, 427-440. doi:10.1002/path.6245. https://pubmed.ncbi.nlm.nih.gov/38229567/
9. Yang, Di, Bai, Fengxiang, Lopez Martinez, David, Cao, Lily Jiaqi, Cohn, Martin A. 2024. PP2A licenses the FANCD2/FANCI complex for chromosome loading. In Cell reports, 43, 114971. doi:10.1016/j.celrep.2024.114971. https://pubmed.ncbi.nlm.nih.gov/39535917/
10. Li, Xujun, Liu, Jiangyi. 2023. FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma. In BMC cancer, 23, 179. doi:10.1186/s12885-023-10626-7. https://pubmed.ncbi.nlm.nih.gov/36814203/
Quality Control Standard
Sperm Test
Pre-cryopreservation: Measurement of sperm concentration, determination of sperm viability.
Post-cryopreservation: A vial of cryopreserved sperms is selected for in-vitro fertilization from each batch.
Environmental Standards:SPF
Available Region:Global
Source:Cyagen