The researchers used a mouse model of FA that lacks Fancd2
, a key protein in the FA pathway.
Solovieva et al., "Reduced FANCD2
influences spontaneous SCE and RAD51 foci formation in uveal melanoma and Fanconi anaemia," Oncogene, vol.
Most FA patients harbour homozygous or double heterozygous mutations in the FANCA (60-65%), FANCC (10-15%), FANCG (~10%) or FANCD2
(3-6%) genes, while the minority of FA patients are characterised by mutations distributed in the remaining 12 FANC genes (3).
Genes Tested AtP ALK APC ATM BAP1 BRCA2 BRIP1 BUB1B CDC73 CDH1 CEP57 CHEK2 CYLD DDB2 DICER1 ERCC3 ERCC4 ERCC5 EXT1 EXT2 FANCD2
FANCE FANCF FANCG FANCI GATA2 GPC3 HNF1A HOXB13 HRAS MLH1 MHS2 MSH6 MUTYH NBN PHOX2B PMS1 PMS2 PPM1D PRF1 RAD51D RBI RECQL4 RET RHBDF2 SDHC SDHD SLX4 SMAD4 SMARCA4 TP53 TSC1 TSC2 VHL WT1 BARD1 BLM BMPR1A BRCA1 CDK4 CDKN1C CDKN2A CEBPA DI53L2 EGFR EPCAM ERCC2 EZH2 FANCA FANCB FANCC FANCL FANCM FH FLCN KIT MAX MEN1 MET NF1 NF2 NSD1 PALB2 PRKAR1A PTCH1 PTEN RAD51C RUN XI SBDS SDHAF2 SDHB SMARCB1 STK11 5UFU TMEM127 WRN XPA XPC This chart shows all 98 cancer susceptible genes included in this new test.
RING, RING (really interesting new gene) domain; PALB2, partner and localizer of BRCA2; BRCT, BRCA1 c-terminus domain; NPM1, nucleophosmin 1; POLH, DNA polymerase eta; FANCD2
, Fanconi anemia complementation group D2; SHFM1/DSS, 26S proteasome complex subunit protein DSS (deleted in split hand/split foot), encoded by the gene SHFM1; BRC repeats, breast cancer repeats; NES, nuclear export signal.
The milestone of DNA strand exchange is RAD51 protein which is closely related to other tumour suppressor genes such as TP53, ATM, BRCA1, BLM, and FANCD2
. Preclinical studies showed that BRCA2 disruptions sensitize mice embryos to ionising radiation , which was previously observed in RAD51 knockout mice embryos .
Similar studies have confirmed the activation of NBN  and added observations showing activation of three other proteins involved in DNA repair, RPA2 , FANCD2
, and FANCI .
Probeset ID Gene name Gene symbol 234278_at Epidermal growth EPS15 factor receptor pathway substrate 15 242560_at Fanconi anemia, FANCD2
complementation group D2 204484_at Phosphoinositide-3- PIK3C2B kinase, class 2, beta polypeptide 231830_x_at RAB11 family RAB11FIP1 Interacting protein 1 (class I) 235395_at SEC63-like (S.
HCC with recurrence exhibited enrichment of upregulated genes mapping to signaling or disease pathways associated with cell cycle regulators (CDKN2B, E2F2, E2F5, GNL3, HDAC2, MDM2, MYC, and PA2G4), including the genes that encode the proteins that control molecular mechanisms of cancer (FANCD2
, FZD3, PLCB1, and PMAIP1).
ATM-dependent phosphorylation of BRCA1, NBS1 and two additional players in the NBS1 branch of the pathway the SMC1, a chromosomal structural maintenance protein and FANCD2
, a Fanconi anemia complementation group D2 protein, both are needed for an intact intra-S phase checkpoint (Shiloh et al., 2003; Andrea et al., 2003).
Scientists had shown previously that DNA repair was much less efficient when FANCI and FANCD2
lack the single ubiquitin.