DNA damage induces nuclear actin filament assembly by Formin-2 and Spire-1/2 that promotes efficient DNA repair

摘要

In animals, plants, and other eukaryotic organisms, a cell's DNA is contained within a structure called the nucleus, which separates it from the rest of the interior of the cell. Filaments of a protein called actin are normally found outside the nucleus, where they help give the cell its overall shape and organize its contents. However, these filaments can sometimes form inside the nucleus in response to a sudden increase in heat or another type of stress. However, it was not clear what role these actin filaments play in the nucleus because it was difficult to distinguish them from the actin filaments that form in other parts of the cell. Researchers have recently developed new techniques to study actin filaments inside the nuclei of live cells under a microscope, using fluorescent protein tags. Here, Belin et al.—including some of the researchers involved in the previous work—used this technique to investigate whether DNA damage causes actin filaments to form in the nuclei of human cells. The experiments show that DNA damage does indeed lead to the formation of actin filaments in the nucleus. In a structure within the nucleus called the nucleolus, the actin filaments are short. However, in the rest of the nucleus, the actin forms long filaments and dense clusters. Cells that contained lower levels of actin were less able to repair their DNA than normal cells. Belin et al. also identified three proteins—called Formin-2, Spire-1, and Spire-2—that assemble the actin filaments in the nucleus. These proteins are also required to make actin filaments in other parts of the cell. The experiments show that the level of Formin-2 increases in the nucleus after DNA damage, and that the DNA of cells lacking this protein is more severely damaged. Belin et al.'s findings reveal a new role for actin in the repair of DNA and the next challenge is to understand the details of how this works.