| Autor: |
Doss RM; Department of Biology, University of Colorado at Colorado Springs, Colorado Springs, CO 80918., Xhunga S; Department of Biology, University of Colorado at Colorado Springs, Colorado Springs, CO 80918., Klimczak D; Department of Biology, University of Colorado at Colorado Springs, Colorado Springs, CO 80918., Cameron M; Department of Biology, University of Colorado at Colorado Springs, Colorado Springs, CO 80918., Verlare J; Department of Biology, University of Colorado at Colorado Springs, Colorado Springs, CO 80918., Wolkow TD; Department of Biology, University of Colorado at Colorado Springs, Colorado Springs, CO 80918. |
| Abstrakt: |
Schizosaccharomyces pombe delays entry into mitosis following G 2 microtubule damage. This pathway is dependent on Rad26 ATRIP , the regulatory subunit of the Rad26 ATRIP /Rad3 ATR DNA damage response (DDR) complex. However, this G 2 microtubule damage response pathway acts independently of the G 2 DNA damage checkpoint pathway. To identify other proteins in this G 2 microtubule damage pathway, we previously screened a cDNA overexpression library for genes that rescued the sensitivity of rad26Δ cells to the microtubule poison thiabendazole. A partial cDNA fragment encoding only the C-terminal regulatory region of the microtubule bundling protein Ase1 PRC1 was isolated. This fragment lacks the Ase1 PRC1 dimerization and microtubule binding domains and retains the conserved C-terminal unstructured regulatory region. Here, we report that ase1Δ cells fail to delay entry into mitosis following G 2 microtubule damage. Microscopy revealed that Rad26 ATRIP foci localized alongside Ase1 PRC1 filaments, although we suggest that this is related to microtubule-dependent double strand break mobility that facilitates homologous recombination events. Indeed, we report that the DNA repair protein Rad52 co-localizes with Rad26 ATRIP at these foci, and that localization of Rad26 ATRIP to these foci depends on a Rad26 ATRIP N-terminal region containing a checkpoint recruitment domain. To our knowledge, this is the first report implicating Ase1 PRC1 in regulation of the G 2 /M transition.
Competing Interests: We declare there is no conflict of interest to report. |
