The cell cycle timing of centromeric chromatin assembly in Drosophila meiosis is distinct from mitosis yet requires CAL1 and CENP-C

PLoS Biol. 2012;10(12):e1001460. doi: 10.1371/journal.pbio.1001460. Epub 2012 Dec 27.

Abstract

CENP-A (CID in flies) is the histone H3 variant essential for centromere specification, kinetochore formation, and chromosome segregation during cell division. Recent studies have elucidated major cell cycle mechanisms and factors critical for CENP-A incorporation in mitosis, predominantly in cultured cells. However, we do not understand the roles, regulation, and cell cycle timing of CENP-A assembly in somatic tissues in multicellular organisms and in meiosis, the specialized cell division cycle that gives rise to haploid gametes. Here we investigate the timing and requirements for CID assembly in mitotic tissues and male and female meiosis in Drosophila melanogaster, using fixed and live imaging combined with genetic approaches. We find that CID assembly initiates at late telophase and continues during G1 phase in somatic tissues in the organism, later than the metaphase assembly observed in cultured cells. Furthermore, CID assembly occurs at two distinct cell cycle phases during male meiosis: prophase of meiosis I and after exit from meiosis II, in spermatids. CID assembly in prophase I is also conserved in female meiosis. Interestingly, we observe a novel decrease in CID levels after the end of meiosis I and before meiosis II, which correlates temporally with changes in kinetochore organization and orientation. We also demonstrate that CID is retained on mature sperm despite the gross chromatin remodeling that occurs during protamine exchange. Finally, we show that the centromere proteins CAL1 and CENP-C are both required for CID assembly in meiosis and normal progression through spermatogenesis. We conclude that the cell cycle timing of CID assembly in meiosis is different from mitosis and that the efficient propagation of CID through meiotic divisions and on sperm is likely to be important for centromere specification in the developing zygote.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Centromere / metabolism*
  • Centromere Protein A
  • Chromatin Assembly and Disassembly*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosome Segregation
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / metabolism
  • Female
  • G1 Phase
  • Histones / metabolism
  • Larva / cytology
  • Male
  • Meiosis*
  • Mitosis*
  • Models, Biological
  • Protein Transport
  • Spermatids / cytology
  • Spermatids / metabolism
  • Telophase
  • Time Factors

Substances

  • CENP-C protein, Drosophila
  • Cal1 protein, Drosophila
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone
  • Cid protein, Drosophila
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Histones
  • centromere protein C