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Comments on Seung-hwan Kim et al. (2005) International Worm Meeting "The kinetochore components HCP-1 and HCP-2 promote S phase progression when chromosomes are damaged during early embryogenesis in C. elegans." (0)
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Seung-hwan Kim, & W Matthew Michael (2005). The kinetochore components HCP-1 and HCP-2 promote S phase progression when chromosomes are damaged during early embryogenesis in C. elegans presented in International Worm Meeting. Unpublished information; cite only with author permission.
We performed a systematic screen using RNAi of 4149 genes on chromosome V to identify those genes whose loss-of-function by RNAi causes sensitivity to two DNA damaging agents, methyl methanesulfonate (MMS) and ultra violet (UV) light. These MMS- and UV-sensitive genes fell into several categories, such as cell cycle and checkpoint regulators, DNA repair genes, and meiotic genes. Among the genes recovered in this screen were hcp-1 and hcp-2, which have previously been shown to function in kinetochore assembly. Depletion of either hcp-1 or hcp-2 by RNAi caused two phenotypes that were dependent upon DNA damage. One, progression through S phase in the early cleavage cycles was significantly delayed. Two, nuclear morphology in early embryos was perturbed in that nuclei were enlarged and of abnormal shape. These findings link kinetochore assembly to S phase progression during the DNA damage response and suggest a feedback mechanism whereby DNA synthesis is slowed when kinetochore assembly is attenuated on damaged chromosomes.
Affiliation:
- Molecular & Cellular Biology, Harvard University, Cambridge, MA.