Mitotic remodeling of the replicon and chromosome structure

Cell. 2005 Dec 2;123(5):787-801. doi: 10.1016/j.cell.2005.08.045.

Abstract

Animal cloning by nuclear-transfer experiments frequently fails due to the inability of transplanted nuclei to support normal embryonic development. We show here that the formation of mitotic chromosomes in the egg context is crucial for adapting differentiated nuclei for early development. Differentiated erythrocyte nuclei replicate inefficiently in Xenopus eggs but do so as rapidly as sperm nuclei if a prior single mitosis is permitted. This mitotic remodeling involves a topoisomerase II-dependent shortening of chromatin loop domains and an increased recruitment of replication initiation factors onto chromatin, leading to a short interorigin spacing characteristic of early developmental stages. It also occurs within each early embryonic cell cycle and dominantly regulates initiation of DNA replication for the subsequent S phase. These results indicate that mitotic conditioning is crucial to reset the chromatin structure of differentiated adult donor cells for embryonic DNA replication and suggest that it is an important step in nuclear cloning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Cell Extracts / chemistry
  • Cell Nucleus / physiology
  • Cell Nucleus / ultrastructure
  • Chromosomes / chemistry*
  • Chromosomes / metabolism
  • Cloning, Organism*
  • DNA Replication*
  • DNA Topoisomerases, Type II / metabolism
  • Erythrocytes / cytology
  • Erythrocytes / metabolism
  • Histones / metabolism
  • Humans
  • Male
  • Mitosis / physiology*
  • Nuclear Transfer Techniques
  • Nucleic Acid Conformation
  • Replication Origin
  • Replicon*
  • Spermatozoa / cytology
  • Spermatozoa / metabolism
  • Xenopus laevis / embryology*
  • Xenopus laevis / physiology

Substances

  • Cell Extracts
  • Histones
  • DNA Topoisomerases, Type II