In particular, Deng and his colleagues wanted to examine the effects of dysfunctional BRCA1 on the cell cycle. Deng says that hints from work conducted in other labs suggested that the level of BRCA1 expression changes during the cell cycle and therefore could be involved with unchecked cellular proliferation in familial breast tumors. They used mouse embryonic fibroblast cells (MEFs) to examine how a disabled, exon 11-deficient BRCA1 gene would affect the two major cell cycle checkpoints, G1-S and G2-M. The G1-S checkpoint arrests cells in G1, thereby preventing damaged DNA from being duplicated, and the G2-M checkpoint prevents damaged chromosomes from segregating and entering mitosis.
The researchers found that while the G1-S checkpoint remained intact, they discovered "quite surprisingly, that the mutated cells completely lost their G2-M cell-cycle checkpoint," Deng says. Also, about 25 percent of the cells had abnormal numbers of centrosomes that had formed abnormal mitotic spindles. ...
