Research from Professor Anton Gartner’s group in the Centre for Gene Expression and Regulation has provided new information on the mechanics of cell division. Published today in Nature Communications, the work shows the role of a particular protein in this process that may have implications in understanding some types of breast and ovarian cancer.

LEM-3 is phosphorylated at the midbody.

Faithful chromosome segregation requires all connections that physically link them to be removed before cells divide; failure to do so may lead to the severing of chromosomes, prevent cell division or cause aneuploidy (where there is the wrong number of chromosomes in a cell). Not only must connections between chromosomes be removed prior to segregation, but so must DNA connections that link chromatids (two chromatids form a chromosome). These DNA connections include DNA repair intermediates, points at which chromosomes have become intertwined, and stretches of DNA that have not yet been copied.

Proposed model for chromatin-bridge processing by
the midbody associated LEM-3 nuclease

Using C. elegans embryos Ye Hong, in a collaboration between the Gartner and Labib labs in Dundee, and Verena Jantsch in Vienna demonstrated a new mechanism of how these DNA linkages are processed just before cells divide. Ye showed that the conserved LEM-3/Ankle1 nuclease, a protein that sculptures abnormal DNA, is key to a new genome integrity mechanism. Ye et al., demonstrated that LEM-3 acts right at the point where cells divide, thus providing a last chance saloon mechanism for cells to fix their DNA. Ye Hong worked out how the LEM-3 nuclease is regulated to fulfil this function. These studies are not only important for defining a new genome maintenance mechanism, but also because the LEM-3 found in C. elegans has a human version called Ankle1 that has recently been implicated to be involved in breast and ovarian cancer. The findings from this study provide a clue to how such cancers might be prevented in human cells.

The work in Dundee was funded by the Wellcome Trust and the MRC.