The kinetochore interaction network (KIN) of ascomycetes

Abstract

Chromosome segregation relies on coordinated activity of a large assembly of proteins, the kinetochore interaction network (KIN). How conserved the underlying mechanisms driving the epigenetic phenomenon of centromere and kinetochore assembly and maintenance are remains unclear, even though various eukaryotic models have been studied. More than 50 different proteins, many in multiple copies, comprise the KIN or are associated with fungal centromeres and kinetochores. Proteins isolated from immune sera recognized centromeric regions on chromosomes and thus were named centromere proteins (CENPs). CENP-A, sometimes called centromere-specific H3 (CenH3), is incorporated into nucleosomes within or near centromeres. The constitutive centromere-associated network (CCAN) assembles on this specialized chromatin, likely based on specific interactions with and requiring presence of CENP-C. The outer kinetochore comprises the Knl1-Mis12-Ndc80 (KMN) protein complexes that connect CCAN to spindles, accomplished by binding and stabilizing microtubules (MTs) and in the process generating load-bearing assemblies for chromatid segregation. In most fungi the Dam1/DASH complex connects the KMN complexes to MTs. Fungi present a rich resource to investigate mechanistic commonalities but also differences in kinetochore architecture. While ascomycetes have sets of CCAN and KMN proteins that are conserved with those of budding yeast or metazoans, searching other major branches of the fungal kingdom revealed that CCAN proteins are poorly conserved at the primary sequence level. Several conserved binding motifs or domains within KMN complexes have been described recently, and these features of ascomycete KIN proteins are shared with most metazoan proteins. In addition, several ascomycete-specific domains have been identified here.

• CCAN
• centromere
• Dam1
• histones
• kinetochore
• KMN
• Neurospora crassa
• Zymoseptoria tritici

Acknowledgments

I thank all members of my laboratory for fruitful discussions, and Jason Stajich and Kaustuv Sanyal for input about fungal Dam1 and CCAN complexes, respectively. I also thank one anonymous reviewer for helpful comments and corrections that made this a better manuscript. I apologize to those authors whose work was not cited because of space concerns; this is a fast-moving field, and only literature published by Aug 2015 was included here. This manuscript was prepared during a sabbatical in the laboratory of Eva H. Stukenbrock at the Max-Planck-Institut für Evolutionsbiologie in Plön, and I thank her and members of the MPI for discussions and their hospitality during my stay. Financial support through a grant from the NIH ( R01GM097637) is gratefully acknowledged.