Esc2 and Sgs1 act in functionally distinct branches of the homologous recombination repair pathway in Saccharomyces cerevisiae

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

SN - 1059-1524

VL - 20

SP - 1683

EP - 1694

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

IS - 6

ER -