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 language | English (US) |
|---|---|
| Pages (from-to) | 618-628 |
| Number of pages | 11 |
| Journal | DNA Repair |
| Volume | 5 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 10 2006 |
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Keywords
- DNA damage
- DNA recombination
- ESC4
- Rad55
- RTT107
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Esc4/Rtt107 and the control of recombination during replication
AU - Chin, Jodie K.
AU - Bashkirov, Vladimir I.
AU - Heyer, Wolf Dietrich
AU - Romesberg, Floyd E.
PY - 2006/5/10
Y1 - 2006/5/10
N2 - 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.
AB - 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.
KW - DNA damage
KW - DNA recombination
KW - ESC4
KW - Rad55
KW - RTT107
UR - http://www.scopus.com/inward/record.url?scp=33646120588&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646120588&partnerID=8YFLogxK
U2 - 10.1016/j.dnarep.2006.02.005
DO - 10.1016/j.dnarep.2006.02.005
M3 - Article
VL - 5
SP - 618
EP - 628
JO - DNA Repair
JF - DNA Repair
SN - 1568-7864
IS - 5
ER -