| Outline of Final Research Achievements |
RECQL4 is mutated in Rothmund Thomson syndrome, characterized by cancer susceptibility. We find RECQL4 is a microtubule-associated protein (MAP) required for chromosome alignment to the metaphase plate. We detect that the patient cells, lacking RECQL4 protein, show chromosome misalignment, proposing that the chromosome misalignment may be the cause of the disease. We also find VPS72, one of the chromatin-remodeling complex proteins, is essential for postmitotic nuclear re-assembly. Mechanistically, VPS72 binds to postmitotic chromatin and incorporate a histone variant H2AZ on chromatin that enables to assemble compact and functional nuclei. SART1 is previously shown to be important for pre-mRNA splicing and mitotic progression, but the mitotic role of SART1 have not been characterized in detail. We identify SART1 is also a MAP localizing uniquely to spindle poles. We show SART1 mechanistically recruits pericentriolar material proteins and contributes to spindle pole assembly.
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