Isolation of recombinant DNA elongation proteins

Methods Mol Biol. 2009:521:345-59. doi: 10.1007/978-1-60327-815-7_19.

Abstract

This chapter summarizes isolation procedures of four recombinant human proteins crucial for DNA replication: (a) the replicative DNA polymerase (pol) delta, (b) proliferating cell nuclear antigen (PCNA), (c) replication protein A (RP-A), and (d) replication factor C (RF-C). Pol delta is a four-subunit enzyme essential for replication of the lagging strand and possibly of the leading strand. PCNA is a central player important for coordination of the complex network of proteins interacting at the replication fork. RP-A is single-strand DNA-binding protein involved in DNA replication, DNA repair, DNA recombination, and checkpoint control. RF-C as a clamp loader is required for loading of PCNA onto double-stranded DNA and therefore enables PCNA-dependent elongation by pol delta and pol epsilon. To reconstitute the intact pol delta and RF-C, a baculovirus expression system is used, where insect cells are infected with baculoviruses, each coding for one of the four or five subunits of pol delta or RF-C, respectively. We also present two easy methods to isolate the homotrimeric human PCNA and the heterotrimeric human RP-A from an Escherichia coli expression system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baculoviridae / genetics
  • Cell Line
  • Chromatography, Affinity / methods
  • DNA Polymerase III / genetics
  • DNA Polymerase III / isolation & purification*
  • DNA Polymerase III / metabolism
  • DNA Replication / physiology*
  • Escherichia coli / genetics
  • Humans
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / isolation & purification*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Protein Subunits
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Replication Protein A / genetics
  • Replication Protein A / isolation & purification*
  • Replication Protein A / metabolism
  • Replication Protein C / genetics
  • Replication Protein C / isolation & purification*
  • Replication Protein C / metabolism
  • Spodoptera / genetics

Substances

  • Proliferating Cell Nuclear Antigen
  • Protein Subunits
  • RPA1 protein, human
  • Recombinant Proteins
  • Replication Protein A
  • DNA Polymerase III
  • Replication Protein C