Mediating DNA damage is a crucial process, and one of the most important cellular guards against cancer. In response to DNA damage, sophisticated cellular machinery is recruited to repair the breaks, and if it fails, the cell is committed to death. Decades of research have elucidated the key players, and 53BP1 antibodies have revealed the protein to be central in the formation of DNA damage foci - regions flanking the chromatin of DSBs to which DNA repair factors are drafted.
In order to translocate to the nucleus, 53BP1 and other proteins must pass through nuclear pore complexes (NPCs), large channels that span the nuclear envelope. NPCs are made up of more than 30 types of nucleoporins, specialized proteins that facilitate the specific transport of proteins across the membrane. Recent evidence suggests that one nucleoporin in particular, NUP153, is essential for the localization of 53BP1 to the nucleus and the subsequent maintenance of genomic integrity. Using an siRNA screen, Moudry, et al. discovered the dependency of 53BP1 on NUP153, and began to characterize this unrecognized pathway. Their work establishes nuclear trafficking as a novel level of regulation involved in DNA damage repair network and cell fate decision making, creating potential for therapeutic targets. Additional work is needed to characterize the 53BP1/NUP153 pathway as well as those that involve other genome surveillance proteins such as FANCD2, RAD51, and BRCA1.
Moudry P, et al. Nucleoporin NUP153 guards genome integrity by promoting nuclear import of 53BP1. Cell Death and Differentiation 2011; 1-10. [PMID: 22075984]
Novus Biologicals offers NUP153 reagents for your research needs including: