Esc4/Rtt107 and the control of recombination during replication

Jodie K. Chin, Vladimir I. Bashkirov, Wolf Dietrich Heyer, Floyd E. Romesberg

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

When replication forks stall during DNA synthesis, cells respond by assembling multi-protein complexes to control the various pathways that stabilize the replication machinery, repair the replication fork, and facilitate the reinitiation of processive DNA synthesis. Increasing evidence suggests that cells have evolved scaffolding proteins to orchestrate and control the assembly of these repair complexes, typified in mammalian cells by several BRCT-motif containing proteins, such as Brca1, Xrcc1, and 53BP1. In Saccharomyces cerevisiae, Esc4 contains six such BRCT domains and is required for the most efficient response to a variety of agents that damage DNA. We show that Esc4 interacts with several proteins involved in the repair and processing of stalled or collapsed replication forks, including the recombination protein Rad55. However, the function of Esc4 does not appear to be restricted to a Rad55-dependent process, as we observed an increase in sensitivity to the DNA alkylating agent methane methylsulfonate (MMS) in a esc4Δ rad55Δ mutant, as well as in double mutants of esc4Δ and other recombination genes, compared to the corresponding single mutants. In addition, we show that Esc4 forms multiple nuclear foci in response to treatment with MMS. Similar behavior is also observed in the absence of damage when either of the S-phase checkpoint proteins, Tof1 or Mrc1, is deleted. Thus, we propose that Esc4 associates with ssDNA of stalled forks and acts as a scaffolding protein to recruit and/or modulate the function of other proteins required to reinitiate DNA synthesis.

Original languageEnglish (US)
Pages (from-to)618-628
Number of pages11
JournalDNA Repair
Volume5
Issue number5
DOIs
StatePublished - May 10 2006

Fingerprint

Genetic Recombination
Proteins
DNA
Methane
Repair
S Phase Cell Cycle Checkpoints
Amino Acid Motifs
Alkylating Agents
DNA Damage
Saccharomyces cerevisiae
Yeast
Machinery
Genes
Cells
Processing

Keywords

  • DNA damage
  • DNA recombination
  • ESC4
  • Rad55
  • RTT107

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Chin, J. K., Bashkirov, V. I., Heyer, W. D., & Romesberg, F. E. (2006). Esc4/Rtt107 and the control of recombination during replication. DNA Repair, 5(5), 618-628. https://doi.org/10.1016/j.dnarep.2006.02.005

Esc4/Rtt107 and the control of recombination during replication. / Chin, Jodie K.; Bashkirov, Vladimir I.; Heyer, Wolf Dietrich; Romesberg, Floyd E.

In: DNA Repair, Vol. 5, No. 5, 10.05.2006, p. 618-628.

Research output: Contribution to journalArticle

Chin, JK, Bashkirov, VI, Heyer, WD & Romesberg, FE 2006, 'Esc4/Rtt107 and the control of recombination during replication', DNA Repair, vol. 5, no. 5, pp. 618-628. https://doi.org/10.1016/j.dnarep.2006.02.005
Chin, Jodie K. ; Bashkirov, Vladimir I. ; Heyer, Wolf Dietrich ; Romesberg, Floyd E. / Esc4/Rtt107 and the control of recombination during replication. In: DNA Repair. 2006 ; Vol. 5, No. 5. pp. 618-628.
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