The Fml1-MHF complex suppresses inter-fork strand annealing in fission yeast

Io Nam Wong1, Jacqueline Ps Neo1, Judith Oehler1

  • 1Department of Biochemistry, University of Oxford, Oxford, United Kingdom.

Elife
|December 20, 2019
PubMed

Insights

The DNA helicase Fml1 suppresses genomic deletions caused by inter-fork strand annealing (IFSA). This suppression requires Fml1

Area of Science:

  • Molecular Biology
  • Genetics
  • DNA Replication

Background:

  • Inter-fork strand annealing (IFSA) can cause genomic deletions during DNA replication fork convergence.
  • The FANCM-related DNA helicase Fml1 was previously suggested as a potential suppressor of IFSA.

Purpose of the Study:

  • To confirm Fml1's role in suppressing IFSA.
  • To elucidate the mechanism by which Fml1 suppresses IFSA.

Main Methods:

  • Genetic analysis to confirm Fml1's suppressor function.
  • Biochemical assays to assess Fml1's catalytic activity and interaction with Mhf1-Mhf2.
  • In vitro assays to demonstrate Fml1's role in regressed fork restoration.

Main Results:

  • Fml1 was confirmed to suppress IFSA.
  • Fml1's suppression activity is dependent on its catalytic activity and interaction with Mhf1-Mhf2 via its C-terminal domain.
  • Fml1 was shown to catalyze regressed fork restoration in vitro, providing a mechanism for IFSA suppression.

Conclusions:

  • Fml1 is a key suppressor of IFSA-mediated genomic deletions.
  • Fml1 functions by restoring regressed replication forks, preventing aberrant DNA repair pathways.
  • Understanding Fml1's mechanism provides insights into maintaining genome stability during DNA replication.

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