LAUSR

Cell cycle progression is characterized by the periodic synthesis and destruction of a host of regulatory proteins that produces oscillating waves of activity, such as cyclin-dependent kinase (Cdk) activity, to drive unidirectional advancement through the cell cycle. These waves of activity also ensure cells select the optimal mechanism to repair damaged DNA. Cells utilize two major DNA repair pathways, non-homologous end joining (NHEJ) and homologous recombination (HR).[1] NHEJ is a rapid and efficient means of repair, but is potentially mutagenic. HR, in contrast, utilizes homologous DNA sequences as a template for faithful repair and is limited to parts of the cell cycle (mid-late S and G2) when sister chromatids are present in the cell and elevated Cdk activity promotes the use of HR. Sister chromatids are of course present in mitosis as well. However, the faithful segregation of chromosomes in mitosis is critical for genome stability and chromosomes condense to facilitate the movement of such large units of DNA. It is critical that no physical links between sister chromatids, such as HR intermediates, are present at anaphase, which would lead to chromosome mis-segretion and/or DNA damage. Thus, although damage occurring in mitosis is sensed, mitotic cells actively inhibit DNA repair and also induce mechanisms specifically tasked with resolving any intermediates or other linkages that remain in early mitotic chromosomes.[1] Interestingly, while Cdk activity promotes HR in S and G2, the higher levels of Cdk activity inmitosis ultimately blocks both cell cycle checkpoint signaling and DNA repair.[1] In an Ideas and Speculation article in this issue of BioEssays, Machín and Ayra-Plasencia discuss their recent discovery that challenges long held dogmas of mitotic progression and mitotic responses to DNA damage.[2] First, the authors found that DNA damage occurring during telophase in budding yeast elicits a checkpoint-mediated mitotic delay and is repaired by HR.[3] Biochemically, telophase may represent a unique window in mitosis that is permissive for HR-mediated repair. The triggering of cyclin destruction at anaphase onset leads to loss of Cdk activity and the dephosphorylation of Cdk substrates. It is conceivable that differential rates or timing of substrate dephos-