Emerging functions of the Fanconi anemia pathway at a glance

R Sumpter Jr, B Levine - Journal of cell science, 2017 - journals.biologists.com
Journal of cell science, 2017journals.biologists.com
Fanconi anemia (FA) is a rare disease, in which homozygous or compound heterozygous
inactivating mutations in any of 21 genes lead to genomic instability, early-onset bone
marrow failure and increased cancer risk. The FA pathway is essential for DNA damage
response (DDR) to DNA interstrand crosslinks. However, proteins of the FA pathway have
additional cytoprotective functions that may be independent of DDR. We have shown that
many FA proteins participate in the selective autophagy pathway that is required for the …
Abstract
Fanconi anemia (FA) is a rare disease, in which homozygous or compound heterozygous inactivating mutations in any of 21 genes lead to genomic instability, early-onset bone marrow failure and increased cancer risk. The FA pathway is essential for DNA damage response (DDR) to DNA interstrand crosslinks. However, proteins of the FA pathway have additional cytoprotective functions that may be independent of DDR. We have shown that many FA proteins participate in the selective autophagy pathway that is required for the destruction of unwanted intracellular constituents. In this Cell Science at a Glance and the accompanying poster, we briefly review the role of the FA pathway in DDR and recent findings that link proteins of the FA pathway to selective autophagy of viruses and mitochondria. Finally, we discuss how perturbations in FA protein-mediated selective autophagy may contribute to inflammatory as well as genotoxic stress.
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