| Outline of Final Research Achievements |
We aimed to define the role of centromere protein A (CENP-A), a histone H3 variant, as a key mediator of this crosstalk. CENP-A is a constituent of the centromere-specific chromatin essential for the assembly of the kinetochore, a proteinaceous structure that provides the connection between chromosomes and spindle microtubules. CENP-A plays a crucial role in centromere identity and kinetochore assembly. Interestingly, CENP-A also localizes to DNA double-strand breaks (DSBs) but not at other DNA lesions. We found that CENP-A depleted cells were highly sensitive to ionizing irradiation, but over-expression of CENP-A reduced radiosensitivity. We identified several novel proteins that associate with CENP-A specifically when DSBs occur. We also found BUB1, a spindle checkpoint component, is present at DSBs. Our results suggest the role of CENP-A in the activation of the spindle checkpoint in response to failed DNA damage repair.
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