Research Paper Volume 12, Issue 20 pp 20268—20284
TFG-maintaining stability of overlooked FANCD2 confers early DNA-damage response
- 1 University of Hawaii Cancer Center, University of Hawaii, Honolulu, HI 96813, USA
- 2 Graduate Program of Molecular Biosciences and Bioengineering, University of Hawaii, Honolulu, HI 96813, USA
- 3 Department of Laboratory Medicine and Pathology, Mayo Clinic Foundation, Phoenix, AZ 85054, USA
Received: April 8, 2020 Accepted: May 28, 2020 Published: October 24, 2020https://doi.org/10.18632/aging.103782
How to Cite
Copyright: © 2020 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Emerging Fanconi Anemia (FA) signaling in the field of cancer research annotates the extreme importance of its center player, Fanconi Anemia complementation group D2 (FANCD2) in protecting human cells from going awry. However, a previously-unrecognized form of FANCD2, namely FANCD2-V2, is understudied. We report TRK-Fused Gene (TFG) is critical for roles played by FANCD2-V2 in early responses to DNA damage, but not for FANCD2-V1, the long-known form of FANCD2. FANCD2-V2 forms nuclear foci upon DNA damage, and both its focus appearance and disappearance are earlier than FANCD2-V1. The amino acid/aa 5-100 of TFG and the aa1437-1442 of FANCD2-V2 were identified to contribute to their interaction, which maintains the steady-state level of FANCD2-V2 protein. TFGΔaa5-100 or FANCD2-V2Δaa1437-1442-carrying cells could not show timely focus formation of FANCD2-V2 upon DNA damage and gained carcinogenicity over time. This study provides a previously-unknown key to unlock in-depth insights into maintaining genome stability, fostering translational studies on preventing, diagnosing and/or treating related diseases.