Double-strand break in the context of "Microhomology-mediated end joining"

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⭐ Core Definition: Double-strand break

DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is constantly modified in cells, by internal metabolic by-products, and by external ionizing radiation, ultraviolet light, and medicines, resulting in spontaneous DNA damage involving tens of thousands of individual molecular lesions per cell per day. DNA modifications can also be programmed.

Molecular lesions can cause structural damage to the DNA molecule, and can alter or eliminate the cell's ability for transcription and gene expression. Other lesions may induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells following mitosis. Consequently, DNA repair as part of the DNA damage response (DDR) is constantly active. When normal repair processes fail, including apoptosis, irreparable DNA damage may occur, that may be a risk factor for cancer.

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👉 Double-strand break in the context of Microhomology-mediated end joining

Microhomology-mediated end joining (MMEJ), also known as alternative nonhomologous end-joining (Alt-NHEJ) is one of the pathways for repairing double-strand breaks in DNA. As reviewed by McVey and Lee, the foremost distinguishing property of MMEJ is the use of microhomologous sequences during the alignment of broken ends before joining, thereby resulting in deletions flanking the original break. MMEJ is frequently associated with chromosome abnormalities such as deletions, translocations, inversions and other complex rearrangements.

There are multiple pathways for repairing double strand breaks, mainly non-homologous end joining (NHEJ), homologous recombination (HR), and MMEJ. NHEJ directly joins both ends of the double strand break and is relatively accurate, although small (usually less than a few nucleotides) insertions or deletions sometimes occur. HR is highly accurate and uses the sister chromatid as a template for accurate repair of the DSB. MMEJ is distinguished from these other repair mechanisms by its use of microhomologous sequences to align the broken strands. This results in frequent deletions and occasionally insertions which are much larger than those produced by NHEJ . MMEJ is completely independent from classical NHEJ and does not rely on NHEJ core factors such as Ku protein, DNA-PK, or Ligase IV.

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Double-strand break in the context of Genome editing

Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly insert genetic material into a host genome, genome editing targets the insertions to site-specific locations. The basic mechanism involved in genetic manipulations through programmable nucleases is the recognition of target genomic loci and binding of effector DNA-binding domain (DBD), double-strand breaks (DSBs) in target DNA by the restriction endonucleases (FokI and Cas), and the repair of DSBs through homology-directed recombination (HDR) or non-homologous end joining (NHEJ).

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Double-strand break in the context of Telomere

A telomere (/ˈtɛləmɪər, ˈtiːlə-/; from Ancient Greek τέλος (télos) 'end' and μέρος (méros) 'part') is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes (see Sequences). Telomeres are a widespread genetic feature most commonly found in eukaryotes. In most or even all species possessing them, they protect the terminal regions of chromosomal DNA from progressive degradation and ensure the integrity of linear chromosomes by preventing DNA repair systems from mistaking the very ends of the DNA strand for a double-strand break.

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Double-strand break in the context of Homology-directed recombination

Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly insert genetic material into a host genome, genome editing targets the insertions to site-specific locations. The basic mechanism involved in genetic manipulations through programmable nucleases is the recognition of target genomic loci and binding of effector DNA-binding domain (DBD), double-strand breaks (DSBs) in target DNA by the restriction endonucleases (FokI and Cas), and the repair of DSBs through homology-directed recombination (HDR) or non-homologous end joining (NHEJ).

The development of CRISPR gene editing in 2015 improved the efficiency, specificity, and practicality of large-scale genome editing.

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LINKED FROM (PARENTS)
← Genome editing ← Microhomology-mediated end joining ← Telomere ← Homology-directed recombination
LINKS TO (CHILDREN)
Chromosome → Cell (biology) → DNA → Genome → Cancer → Metabolism → Ionizing radiation → Ultraviolet light → Medicine → Molecular lesion → Transcription (biology) → Gene expression → Mutation → Daughter cell → Mitosis → Apoptosis →