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Drosophila SUMM4 complex couples insulator function and DNA replication control.

Evgeniya N Andreyeva1, Alexander V Emelyanov1, Markus Nevil2

  • 1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, United States.

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|December 2, 2022
PubMed
Summary
This summary is machine-generated.

The SUMM4 complex, containing SUUR and Mod(Mdg4)-67.2, controls DNA replication timing by acting as a chromatin barrier, delaying replication fork progression through heterochromatin boundaries.

Keywords:
D. melanogasterDNA replicationMod(Mdg4)SUURchromosomesgene expressiongeneticsgenomicsinsulatorpolytene chromosomesunder-replication

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Area of Science:

  • Molecular Biology
  • Genetics
  • Chromatin Biology

Background:

  • Asynchronous chromosome replication dictates genome function, but mechanisms for early vs. late replication timing are unclear.
  • Intercalary heterochromatin replicates late and is underreplicated in polytene chromosomes.
  • The SNF2-related factor SUUR causes locus-specific underreplication in Drosophila.

Purpose of the Study:

  • To elucidate the mechanism by which SUUR regulates DNA replication.
  • To identify SUUR-interacting proteins and characterize their function in replication control.

Main Methods:

  • Developed MS-Enabled Rapid protein Complex Identification (MERCI) to isolate protein complexes.
  • Biochemical assays to measure SUUR ATPase activity.
  • Genetic analysis of SUUR and Mod(Mdg4) mutants in Drosophila.

Main Results:

  • Identified the SUMM4 complex, comprising SUUR and Mod(Mdg4)-67.2.
  • Mod(Mdg4) stimulates SUUR ATPase activity and is crucial for SUUR localization.
  • SUMM4 complex mediates gypsy insulator activity and establishes chromatin barriers.
  • Mutations in SUUR or Mod(Mdg4) reverse intercalary heterochromatin underreplication.
  • SUMM4 delays replication by attenuating fork progression at euchromatin/heterochromatin boundaries.

Conclusions:

  • SUUR, an ATP-dependent motor protein, functions in insulator activity and replication control.
  • Chromatin barriers, mediated by SUMM4, can delay DNA replication.
  • Architectural proteins play a critical role in establishing replication timing.
  • Late replication timing can be established without asynchronous origin firing.