MMEJ repair of double-strand breaks (director’s cut): deleted sequences and alternative endings

By Mitch McVey, Sang Eun Lee. Trends in Genetics, 2008

1,021 citations recorded by the source corpus.

DNA double-strand breaks are normal consequences of cell division and differentiation and must be repaired faithfully to maintain genome stability. Two mechanistically distinct pathways are known to efficiently repair double-strand breaks: homologous recombination and Ku-dependent non-homologous end joining. Recently, a third, less characterized repair mechanism, named microhomology-mediated end joining (MMEJ), has received increasing attention. MMEJ repairs DNA breaks via the use of substantial microhomology and always results in deletions. Furthermore, it probably contributes to oncogenic chromosome rearrangements and genetic variation in humans. Here, we summarize the genetic attributes of MMEJ from several model systems and discuss the relationship between MMEJ and ‘alternative end joining’. We propose a mechanistic model for MMEJ and highlight important questions for future research.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/702403efcd4402a15734979b0fafdee9133b0caa

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In Molecular Biology

1. Feng Zhang
2. Stephen P. Jackson
3. J. Bartek
4. R. Jaenisch
5. A. Cheng
6. A. D’Andrea
7. G. Ira
8. G. McVean

Citations in the corpus

• The DNA-damage response in human biology and disease (2009, background): “A less-well-characterized Ku-independent NHEJ pathway, called microhomology-mediated end-joining (MMEJ) or alternative end-joining, also exists; it always results in sequence deletions 20 .”
• Chapter 1. General introduction (2015, neutral): “MMEJ induces small deletions and causes gene instabilities (75).”
• Plant Mitochondrial Genomes and Recombination (2011, background): “Such end joining can also involve regions of microhomology ( McVey and Lee 2008 ).”
• Genome Engineering of Drosophila with the CRISPR RNA-Guided Cas9 Nuclease (2013, background): “This is likely due to preferential repair by microhomology-mediated end joining (MMEJ) facilitated by the presence of a short repeat adjacent to the YE1 cut site (Figure 2A, underlined in wild-type sequence) (McVey and Lee 2008).”
• Mechanisms of change in gene copy number (2009, background): “These pathways have recently been described in detail elsewher”
• One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome Engineering (2013, positive): “Preferential generation of these alleles is likely caused by a short sequence repeat flanking the DSB (see Figure S2B) consistent with previous reports demonstrating that perfect microhomology sequences flanking the cleavage sites can generate microhomology-mediated precise deletions by end repair m”
• Homologous recombination deficiency: Exploiting the fundamental vulnerability of ovarian cancer (2015, background): “Indeed, upregulation of budding yeast Polθ appears to generate random deletions or insertions of 20 to 200 base pairs (126, 127).”
• Integrating mapping-, assembly- and haplotype-based approaches for calling variants in clinical sequencing applications (2014, background): “Platypus was able to identify 27,608 deletions between 50 and 2,288 bp in length and 481 insertions between 50 28 .”
• Repair Pathway Choices and Consequences at the Double-Strand Break (2015, neutral): “Indeed, upregulation of budding yeast Polυ appears to generate random deletions or insertions of 20–200 bp [76].”