Abstract：
:The back-to-back geometry of sister kinetochores is essential in preventing loss or damage of chromosomes during mitosis. Kinetochore orientation is generated in part by a process of resolving kinetochores at the centromere (centromere resolution) prior to spindle interactions. Because few of the genes required for centromere resolution are known, we used Caenorhabditis elegans to screen for conditional mutants defective in orienting sister kinetochores during mitosis. C. elegans is ideal for such screens because its chromosomes are holocentric. Here we identified an essential gene, cin-4, required for centromere resolution and for removal of cohesin from sites near sister kinetochores during mitosis. Given that compromised cohesin function restores centromere resolution in the absence of cin-4, CIN-4 likely acts to remove cohesin from the CENP-A chromatin enabling centromere resolution. CIN-4 has a high amino acid identity to the catalytic domain of topoisomerase II, suggesting a partial gene duplication of the C. elegans topoisomerase II gene, top-2. Similar to CIN-4, TOP-2 is also required for centromere resolution; however, the loss of TOP-2 is phenotypically distinct from the loss of CIN-4, suggesting that CIN-4 and TOP-2 are topoisomerase II isoforms that perform separate essential functions in centromere structure and function.
journal_name
Geneticsjournal_title
Geneticsauthors
Stanvitch G,Moore LLdoi
10.1534/genetics.107.075275subject
Has Abstractpub_date
2008-01-01 00:00:00pages
83-97issue
1eissn
0016-6731issn
1943-2631pii
178/1/83journal_volume
178pub_type
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