Orc1 controls centriole and centrosome copy number in human cells

Science. 2009 Feb 6;323(5915):789-93. doi: 10.1126/science.1166745.

Abstract

Centrosomes, each containing a pair of centrioles, organize microtubules in animal cells, particularly during mitosis. DNA and centrosomes are normally duplicated once before cell division to maintain optimal genome integrity. We report a new role for the Orc1 protein, a subunit of the origin recognition complex (ORC) that is a key component of the DNA replication licensing machinery, in controlling centriole and centrosome copy number in human cells, independent of its role in DNA replication. Cyclin A promotes Orc1 localization to centrosomes where Orc1 prevents Cyclin E-dependent reduplication of both centrioles and centrosomes in a single cell division cycle. The data suggest that Orc1 is a regulator of centriole and centrosome reduplication as well as the initiation of DNA replication.

Publication types

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

MeSH terms

  • Cell Cycle
  • Cell Line, Tumor
  • Centrioles / physiology*
  • Centrosome / physiology*
  • Cyclin A / metabolism
  • Cyclin E / metabolism
  • Cyclin-Dependent Kinase 2 / metabolism
  • DNA Replication
  • HeLa Cells
  • Humans
  • Kinetics
  • Mutant Proteins / metabolism
  • Origin Recognition Complex / genetics
  • Origin Recognition Complex / metabolism*
  • RNA Interference
  • RNA, Small Interfering
  • Transfection

Substances

  • Cyclin A
  • Cyclin E
  • Mutant Proteins
  • ORC1 protein, human
  • Origin Recognition Complex
  • RNA, Small Interfering
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2