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Chromatin Modifiers Alter Recombination Between Divergent DNA Sequences.

Ujani Chakraborty1, Beata Mackenroth1, David Shalloway1

  • 1Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853-2703.

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|June 22, 2019
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Summary
This summary is machine-generated.

Epigenetic factors and chromatin structure influence DNA repair decisions. Nucleosomes stabilize recombination intermediates, preventing mismatch repair (MMR) and promoting heteroduplex rejection in yeast.

Keywords:
chromatin modifiersheteroduplex rejectionhistone chaperoneshomologous recombinationmismatch repair

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Area of Science:

  • Molecular Biology
  • Genetics
  • Epigenetics

Background:

  • Recombination between divergent DNA sequences is normally prevented by heteroduplex rejection mechanisms.
  • In baker's yeast, mismatch recognition by MutS homolog (MSH) proteins initiates antirecombination.
  • Histone chaperone machinery interacts with mismatch repair (MMR) factors.

Purpose of the Study:

  • To investigate the role of epigenetic factors and chromatin conformation in regulating the decision to reject or repair recombination between divergent DNA substrates.
  • To explore how histone chaperones and deacetylases influence heteroduplex rejection.

Main Methods:

  • Utilized an inverted repeat recombination assay in baker's yeast.
  • Assessed the impact of mutations in histone chaperones (CAF-1, Rtt106) and deacetylases (Sir2, Rpd3, Hst3, Hst4) on recombination outcomes.
  • Performed double-mutant analysis.

Main Results:

  • Histone chaperones CAF-1, Rtt106, and deacetylase Sir2 suppressed heteroduplex rejection.
  • Deacetylases Rpd3, Hst3, and Hst4 promoted heteroduplex rejection.
  • Nucleosomes at DNA lesions stabilize recombination intermediates, competing with MMR factors.

Conclusions:

  • Epigenetic factors and chromatin structure play a critical role in regulating DNA repair pathway choice.
  • Nucleosome positioning and histone modifications influence the balance between heteroduplex rejection and repair.
  • A model is proposed where nucleosomes stabilize recombination intermediates, thereby influencing the competition with MMR factors for heteroduplex processing.