Elg1 forms an alternative PCNA-interacting RFC complex required to maintain genome stability

Curr Biol. 2003 Sep 16;13(18):1583-95. doi: 10.1016/s0960-9822(03)00578-5.


Background: Genome instability is a hallmark of cancer and plays a critical role in generating the myriad of phenotypes selected for during tumor progression. However, the mechanisms that prevent genome rearrangements remain poorly understood.

Results: To elucidate the mechanisms that ensure genome stability, we screened a collection of candidate genes for suppressors of gross chromosomal rearrangements (GCRs) in budding yeast. One potent suppressor gene encodes Elg1, a conserved but uncharacterized homolog of the large RFC subunit Rfc1 and the alternative RFC subunits Ctf18/Chl12 and Rad24. Our results are consistent with the hypothesis that Elg1 forms a novel and distinct RFC-like complex in both yeast and human cells. We find that Elg1 is required for efficient S phase progression and telomere homeostasis in yeast. Elg1 interacts physically with the PCNA homolog Pol30 and the FEN-1 homolog Rad27. The physical and genetic interactions suggest a role for Elg1 in Okazaki fragment maturation. Furthermore, Elg1 acts in concert with the alternative Rfc1-like proteins Rad24 and Ctf18 to enable Rad53 checkpoint kinase activation in response to replication stress.

Conclusions: Collectively, these results reveal that Elg1 forms a novel and conserved alternative RFC complex. Furthermore, we propose that genome instability arises at high frequency in elg1 mutants due to a defect in Okazaki fragment maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • DNA Damage
  • DNA Replication*
  • DNA-Binding Proteins / metabolism
  • Genome*
  • Genomic Instability
  • Humans
  • Macromolecular Substances
  • Molecular Sequence Data
  • Phylogeny
  • Proliferating Cell Nuclear Antigen / metabolism*
  • Protein Binding
  • Replication Protein C
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins
  • Sequence Alignment
  • Transcription Factors / metabolism


  • Carrier Proteins
  • DNA-Binding Proteins
  • Elg1 protein, S cerevisiae
  • Macromolecular Substances
  • Proliferating Cell Nuclear Antigen
  • RFC1 protein, human
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Replication Protein C