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Microhomology Selection for Microhomology Mediated End Joining in Saccharomyces cerevisiae

Kihoon Lee1, Jae-Hoon Ji2, Kihoon Yoon3

  • 1Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. y2k0108@gmail.com.

Genes
|April 11, 2019
PubMed

Insights

Microhomology-mediated end joining (MMEJ) efficiently repairs DNA breaks using short microhomologies. This study reveals MMEJ preferentially selects proximal microhomologies and shows a bias in deletion patterns, offering insights into DNA repair mechanisms.

Area of Science:

  • Molecular Biology
  • Genetics
  • DNA Repair

Background:

  • Microhomology-mediated end joining (MMEJ) repairs DNA double-strand breaks.
  • MMEJ is independent of Ku and RAD52.
  • MMEJ exhibits preferential selection of specific microhomologies.

Purpose of the Study:

  • To define rules governing microhomology selection in MMEJ.
  • To investigate the impact of microhomology length, position, and mismatches on MMEJ.
  • To understand the deletion patterns in MMEJ repair products.

Main Methods:

  • Altering microhomology characteristics (length, position, mismatches) flanking HO endonuclease-induced breaks.
  • Assessing MMEJ frequency and repair product formation.
  • Analyzing the effect of MSH6 deletion on MMEJ.

Main Results:

  • Microhomologies of 8-20 base pairs with ≤20% mismatches efficiently induced MMEJ.
  • MMEJ preferentially selected microhomologies proximal to the break.
  • MMEJ products showed preferential retention of the centromere-proximal side and deletion of telomere-proximal sequences.
  • MSH6 deletion did not affect MMEJ frequency.

Conclusions:

  • Identified optimal microhomology features for efficient MMEJ.
  • Demonstrated MMEJ's preference for proximal microhomologies and asymmetric deletion patterns.
  • Suggests that chromosome topology (linear vs. circular) influences MMEJ deletion profiles.
Keywords:
DNA double strand breakdeletionmicrohomologymicrohomology-mediated end joiningmismatch

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