Multifaceted Fanconi Anemia Signaling.

In 1927 Guido Fanconi described a hereditary condition presenting panmyelopathy accompanied by short stature and hyperpigmentation, now better known as Fanconi anemia (FA). With this discovery the genetic and molecular basis underlying FA has emerged as a field of great interest. FA signaling is crucial in the DNA damage response (DDR) to mediate the repair of damaged DNA.

Fanconi Anemia Signaling and Cancer.

The extremely high cancer incidence associated with patients suffering from a rare human genetic disease, Fanconi anemia (FA), demonstrates the importance of FA genes. Over the course of human tumor development, FA genes perform critical tumor-suppression roles. In doing so, FA provides researchers with a unique genetic model system to study cancer etiology.

FANCD2 and DNA Damage.

Investigators have dedicated considerable effort to understanding the molecular basis underlying Fanconi Anemia (FA), a rare human genetic disease featuring an extremely high incidence of cancer and many congenital defects. Among those studies, FA group D2 protein (FANCD2) has emerged as the focal point of FA signaling and plays crucial roles in multiple aspects of cellular life, especially in the cellular responses to DNA damage. Here, we discuss the recent and relevant studies to provide an updated review on the roles of FANCD2 in the DNA damage response.

Involvement of FANCD2 in Energy Metabolism via ATP5α.

Growing evidence supports a general hypothesis that aging and cancer are diseases related to energy metabolism. However, the involvement of Fanconi Anemia (FA) signaling, a unique genetic model system for studying human aging or cancer, in energy metabolism remains elusive. Here, we report that FA complementation group D2 protein (FANCD2) functionally impacts mitochondrial ATP production through its interaction with ATP5α, whereas this relationship was not observed in the mutant FANCD2 (K561R)-carrying cells.

DNA methylation of METTL7A gene body regulates its transcriptional level in thyroid cancer.

DNA methylation is the best-studied epigenetic mechanism for regulating gene transcription and maintaining genome stability. Current research progress of transcriptional regulation by DNA methylation mostly focuses on promoter region where hypomethylated CpG islands are present transcriptional activity, as hypermethylated CpG islands generally result in gene repression. Recently, the DNA methylation patterns across the gene body (intragenic methylation) have increasingly attracted attention towards their role in transcriptional regulation and efficiency, due to the improvement of numerous genome-wide DNA methylation profiling studies.

Overlooked FANCD2 variant encodes a promising, portent tumor suppressor, and alternative polyadenylation contributes to its expression.

Fanconi Anemia (FA) complementation group D2 protein (FANCD2) is the center of the FA tumor suppressor pathway, which has become an important field of investigation in human aging and cancer. Here we report an overlooked central player in the FA pathway, FANCD2 variant 2 (FANCD2-V2), which appears to perform more potent tumor suppressor-function compared to the known variant of FANCD2, namely, FANCD2-V1. Detailed analysis of the FANCD2 gene structure indicated a proximal and distal polyadenylation site (PAS), associated with V2 and V1 transcripts accordingly.

BLM promotes the activation of Fanconi Anemia signaling pathway.

Mutations in the human RecQ helicase, BLM, causes Bloom Syndrome, which is a rare autosomal recessive disorder and characterized by genomic instability and an increased risk of cancer. Fanconi Anemia (FA), resulting from mutations in any of the 19 known FA genes and those yet to be known, is also characterized by chromosomal instability and a high incidence of cancer. BLM helicase and FA proteins, therefore, may work in a common tumor-suppressor signaling pathway.

Distinct Metabolic Signature of Human Bladder Cancer Cells Carrying an Impaired Fanconi Anemia Tumor-Suppressor Signaling Pathway.

Metabolic profiling has great potential to help the diagnosis and prognosis of cancer patients. Fanconi Anemia (FA) tumor-suppressor signaling has been instrumental in understanding human tumorigenesis. However, this instrumental understanding has never been demonstrated at the metabolic level.