Microhomology-mediated end joining

Definition

Microhomology-mediated end joining (MMEJ) is a DNA repair mechanism that utilizes short, homologous sequences to facilitate the joining of broken DNA ends. This process often occurs when double-strand breaks in DNA are not repaired through the more accurate homologous recombination or non-homologous end joining pathways, leading to potential chromosomal rearrangements and instability.

5 Must Know Facts For Your Next Test

1. MMEJ is particularly error-prone compared to other DNA repair mechanisms, which can lead to mutations or chromosomal rearrangements.
2. This repair pathway is activated primarily during the G1 phase of the cell cycle when homologous recombination is less favorable due to the lack of a sister chromatid.
3. Microhomology regions are typically just a few base pairs long and are essential for aligning the broken ends for repair in MMEJ.
4. The activation of MMEJ can be influenced by factors such as the presence of specific proteins like PARP1, which facilitates the repair process.
5. Increased reliance on MMEJ for DNA repair is often observed in cancer cells, contributing to their genetic diversity and adaptability.

Review Questions

• How does microhomology-mediated end joining differ from other DNA repair mechanisms?
  • Microhomology-mediated end joining differs from other DNA repair mechanisms like homologous recombination and non-homologous end joining primarily in its reliance on short homologous sequences for aligning broken DNA ends. While homologous recombination uses longer sequences for more accurate repairs and non-homologous end joining connects DNA ends directly without requiring homology, MMEJ takes advantage of small microhomologies. This distinction not only affects the accuracy of the repair but also contributes to the potential for mutations and chromosomal instability.
• Evaluate the implications of microhomology-mediated end joining on genomic stability and cancer development.
  • Microhomology-mediated end joining has significant implications for genomic stability as it is an error-prone repair mechanism. The reliance on short homologous sequences can result in deletions or insertions at the site of DNA damage, leading to mutations that may disrupt essential genes or regulatory regions. In cancer development, the increased use of MMEJ allows cancer cells to adapt through genetic changes, promoting tumor progression and heterogeneity. This unstable genome can further contribute to resistance against therapies.
• Synthesize information about how microhomology-mediated end joining operates during different phases of the cell cycle and its impact on cellular outcomes.
  • Microhomology-mediated end joining operates predominantly during the G1 phase of the cell cycle when homologous recombination is less feasible due to the absence of a sister chromatid. This timing affects cellular outcomes significantly because MMEJ's reliance on microhomologies leads to higher mutation rates. Consequently, cells may experience genomic instability, which can trigger oncogenic transformations. The strategic use of MMEJ in G1 allows cells to quickly respond to DNA damage but at the cost of increased risk for aberrant chromosome structures and potential cancer development.

Related terms

Double-strand break: A type of DNA damage where both strands of the DNA helix are severed, creating two free ends that need repair.

Non-homologous end joining: A repair pathway that directly joins the ends of broken DNA without requiring homologous sequences, often resulting in errors.

Chromosomal instability: A condition characterized by an increased rate of mutations or structural changes in chromosomes, often leading to cancer.