The Protein Composition of Mitotic Chromosomes Determined Using Multiclassifier Combinatorial Proteomics

By S. Ohta, Jimi-Carlo Bukowski-Wills, L. Sánchez-Pulido, F. Alves, L. Wood, Zhuo A. Chen, Melpi Platani, L. Fischer, D. Hudson, Chris P. Ponting and 3 more. Cell, 2010

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Summary Despite many decades of study, mitotic chromosome structure and composition remain poorly characterized. Here, we have integrated quantitative proteomics with bioinformatic analysis to generate a series of independent classifiers that describe the ∼4,000 proteins identified in isolated mitotic chromosomes. Integrating these classifiers by machine learning uncovers functional relationships between protein complexes in the context of intact chromosomes and reveals which of the ∼560 uncharacterized proteins identified here merits further study. Indeed, of 34 GFP-tagged predicted chromosomal proteins, 30 were chromosomal, including 13 with centromere-association. Of 16 GFP-tagged predicted nonchromosomal proteins, 14 were confirmed to be nonchromosomal. An unbiased analysis of the whole chromosome proteome from genetic knockouts of kinetochore protein Ska3/Rama1 revealed that the APC/C and RanBP2/RanGAP1 complexes depend on the Ska complex for stable association with chromosomes. Our integrated analysis predicts that up to 97 new centromere-associated proteins remain to be discovered in our data set.

Subfields: Molecular Biology, Spectroscopy

View Paper: https://www.semanticscholar.org/paper/fa61440cafcd19b7b838252086ff5199edab0ba4

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In Molecular Biology

Citations in the corpus

A pathway for mitotic chromosome formation (2018, background): “Chromatin in such cells lacks functional condensin (55, 56) but nonetheless achieves anormal degree of chromatin compaction despite the absence of individualized chromosomes (57).”