FANCD2 is required for the repression of germline transposable elements
Yan Nie, Andrew F. Wilson, Tony DeFalco, Amom Ruhikanta Meetei, Satoshi H. Namekawa, Qishen Pang
Abstract
Fanconi anemia (FA) is a genetic disease associated with bone marrow failure, increased cancer, and severe germline defects, and the FA pathway is known to play a major role in the DNA damage response (DDR) network (Bagby 2003, 2018, Tischkowitz & Hodgson 2003). FA is genetically heterogeneous, with at least 22 complementation groups (FANCA-FANCW) identified thus far (Dong et al. 2015, Sawyer et al. 2015, Knies et al. 2017). Eight of the FA proteins (FANCA, B, C, E, F, G, L, and M) form the FA core complex that functions as an ubiquitin ligase. In response to DNA damage or DNA replication stress, the FA core complex monoubiquitinates two downstream FA proteins, FANCD2 and FANCI, which then recruit the downstream FA proteins and other DNA repair factors, to nuclear loci containing damaged DNA and consequently influence important cellular processes such as DNA replication, cell-cycle control, and DNA damage response and repair (Deans & West 2011, Kottemann & Smogorzewska 2013).