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The Mgs1/WRNIP1 ATPase is required to prevent a recombination salvage pathway at damaged replication forks

Alberto Jiménez-Martín1, Irene Saugar1, Chinnu Rose Joseph2

  • 1Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Cantoblanco, 28049 Madrid, Spain.

Science Advances
|April 15, 2020
PubMed

Insights

The Mgs1 protein prevents a toxic DNA damage bypass pathway. Its absence activates a recombination-driven salvage pathway, crucial for cell survival when DNA replication is blocked.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • DNA damage tolerance (DDT) maintains genome integrity.
  • DDT utilizes error-free template switch recombination or error-prone translesion DNA synthesis.
  • Rad5 is essential for DDT, primarily through template switching.

Purpose of the Study:

  • To investigate the role of Mgs1/WRNIP1 in modulating DNA damage tolerance.
  • To understand how Mgs1 influences alternative DNA damage bypass pathways.

Main Methods:

  • Experiments were conducted using budding yeast models.
  • Genetic analysis involved studying cells lacking Mgs1 and Rad5.
  • Key proteins and pathways like RAD52, RAD59, DNA polymerase δ, PCNA, Esc2, and Elg1 were examined.

Main Results:

  • Eliminating Mgs1 in Rad5-deficient cells activates a Rad52/Rad59-dependent recombination-driven DNA damage bypass pathway.
  • This alternative pathway requires DNA polymerase δ, PCNA modification at K164, Esc2, and Elg1.
  • Mgs1 inhibits this recombination salvage pathway, favoring Rad5-dependent template switching.

Conclusions:

  • Mgs1 prevents a potentially toxic recombination salvage pathway during perturbed DNA replication.
  • By inhibiting this pathway, Mgs1 promotes Rad5-dependent template switching, enhancing genome stability.

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