title: Differential role of CENP-A in the segregation of holocentric C. elegans chromosomes during meiosis and mitosis.
abstract: Two distinct chromosome architectures are prevalent among eukaryotes: monocentric, in which localized centromeres restrict kinetochore assembly to a single chromosomal site, and holocentric, in which diffuse kinetochores form along the entire chromosome length. During mitosis, both chromosome types use specialized chromatin, containing the histone H3 variant CENP-A, to direct kinetochore assembly. For the segregation of recombined homologous chromosomes during meiosis, monocentricity is thought to be crucial for limiting spindle-based forces to one side of a crossover and to prevent recombined chromatids from being simultaneously pulled towards both spindle poles. The mechanisms that allow holocentric chromosomes to avert this fate remain uncharacterized. Here, we show that markedly different mechanisms segregate holocentric chromosomes during meiosis and mitosis in the nematode Caenorhabditis elegans. Immediately prior to oocyte meiotic segregation, outer-kinetochore proteins were recruited to cup-like structures on the chromosome surface via a mechanism that is independent of CENP-A. In striking contrast to mitosis, both oocyte meiotic divisions proceeded normally following depletion of either CENP-A or the closely associated centromeric protein CENP-C. These findings highlight a pronounced difference between the segregation of holocentric chromosomes during meiosis and mitosis and demonstrate the potential to uncouple assembly of outer-kinetochore proteins from CENP-A chromatin.
authors.affiliation: Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, UCSD Biomedical Sciences Graduate Program, UCSD CMM-E, Room 3052, 9500 Gilman Drive, La Jolla, CA 92093-0653, USA.
authors.forename: Joost
authors.initials: J
authors.lastname: Monen
authors.forename: Paul S
authors.initials: PS
authors.lastname: Maddox
authors.forename: Francie
authors.initials: F
authors.lastname: Hyndman
authors.forename: Karen
authors.initials: K
authors.lastname: Oegema
authors.forename: Arshad
authors.initials: A
authors.lastname: Desai
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics*; D000076247:Centromere Protein A; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology*; D020090:Chromosome Segregation; D022004:Chromosome Structures; D018386:Kinetochores / Q000737:chemistry; D008540:Meiosis; D008938:Mitosis; D009865:Oocytes; D021381:Protein Transport
chemical_list: D001324:Autoantigens; D000076247:Centromere Protein A; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone