Esc2 and Sgs1 act in functionally distinct branches of the homologous recombination repair pathway in Saccharomyces cerevisiae
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Esc2 and Sgs1 act in functionally distinct branches of the homologous recombination repair pathway in Saccharomyces cerevisiae. / Mankouri, Hocine W; Ngo, Hien-Ping; Hickson, Ian D.
In: Molecular Biology of the Cell, Vol. 20, No. 6, 01.03.2009, p. 1683-94.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Esc2 and Sgs1 act in functionally distinct branches of the homologous recombination repair pathway in Saccharomyces cerevisiae
AU - Mankouri, Hocine W
AU - Ngo, Hien-Ping
AU - Hickson, Ian D
PY - 2009/3/1
Y1 - 2009/3/1
N2 - Esc2 is a member of the RENi family of SUMO-like domain proteins and is implicated in gene silencing in Saccharomyces cerevisiae. Here, we identify a dual role for Esc2 during S-phase in mediating both intra-S-phase DNA damage checkpoint signaling and preventing the accumulation of Rad51-dependent homologous recombination repair (HRR) intermediates. These roles are qualitatively similar to those of Sgs1, the yeast ortholog of the human Bloom's syndrome protein, BLM. However, whereas mutation of either ESC2 or SGS1 leads to the accumulation of unprocessed HRR intermediates in the presence of MMS, the accumulation of these structures in esc2 (but not sgs1) mutants is entirely dependent on Mph1, a protein that shows structural similarity to the Fanconi anemia group M protein (FANCM). In the absence of both Esc2 and Sgs1, the intra-S-phase DNA damage checkpoint response is compromised after exposure to MMS, and sgs1esc2 cells attempt to undergo mitosis with unprocessed HRR intermediates. We propose a model whereby Esc2 acts in an Mph1-dependent process, separately from Sgs1, to influence the repair/tolerance of MMS-induced lesions during S-phase.
AB - Esc2 is a member of the RENi family of SUMO-like domain proteins and is implicated in gene silencing in Saccharomyces cerevisiae. Here, we identify a dual role for Esc2 during S-phase in mediating both intra-S-phase DNA damage checkpoint signaling and preventing the accumulation of Rad51-dependent homologous recombination repair (HRR) intermediates. These roles are qualitatively similar to those of Sgs1, the yeast ortholog of the human Bloom's syndrome protein, BLM. However, whereas mutation of either ESC2 or SGS1 leads to the accumulation of unprocessed HRR intermediates in the presence of MMS, the accumulation of these structures in esc2 (but not sgs1) mutants is entirely dependent on Mph1, a protein that shows structural similarity to the Fanconi anemia group M protein (FANCM). In the absence of both Esc2 and Sgs1, the intra-S-phase DNA damage checkpoint response is compromised after exposure to MMS, and sgs1esc2 cells attempt to undergo mitosis with unprocessed HRR intermediates. We propose a model whereby Esc2 acts in an Mph1-dependent process, separately from Sgs1, to influence the repair/tolerance of MMS-induced lesions during S-phase.
KW - Cell Cycle Proteins
KW - DEAD-box RNA Helicases
KW - DNA Damage
KW - DNA Repair
KW - DNA, Fungal
KW - Genomic Instability
KW - Mitosis
KW - Mutation
KW - Nuclear Proteins
KW - Protein-Serine-Threonine Kinases
KW - RecQ Helicases
KW - Recombination, Genetic
KW - Saccharomyces cerevisiae
KW - Saccharomyces cerevisiae Proteins
U2 - 10.1091/mbc.E08-08-0877
DO - 10.1091/mbc.E08-08-0877
M3 - Journal article
C2 - 19158388
VL - 20
SP - 1683
EP - 1694
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 6
ER -
ID: 33752813