Extrachromosomal DNA (ecDNA)
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Extrachromosomal DNA

News: Extrachromosomal DNA (ecDNA) is gaining attention in the field of cancer research. Recent studies investigate how it forms and its role in cancer progression and drug resistance.

Fundamentals of Cells and DNA 

  • Human cells contain 23 pairs of chromosomes (total 46 chromosomes).
  • Chromosomes are thread-like structures located in the cell nucleus, made of DNA and proteins.
  • DNA (deoxyribonucleic acid) is a molecule in the nucleus that carries genetic information in the form of genes, which provide instructions for building and maintaining an organism.
  • Most DNA is found in chromosomes (nuclear DNA), but it can also exist as:
    a. Mitochondrial DNA (mtDNA)
    b. Extrachromosomal DNA (ecDNA)
    c. Cell-free DNA (cfDNA)

About extrachromosomal DNA (ecDNA)

ecDNA
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1. ecDNA are small circular DNA fragments that float freely in the nucleus, separate from chromosomes.

2. Formation of ecDNA: It forms when fragments of DNA break away from the main chromosomes due to processes such as chromosomal damage or replication errors. This can occur through mechanisms like:

a. Chromothripsis: A catastrophic event where chromosomes shatter and are reassembled incorrectly, leaving some fragments detached.
b. Replication Errors: Mistakes during DNA replication can result in fragments being excluded from chromosomes.

3. Role of ecDNA in Cancer:

  • ecDNA is present in up to 90% of certain tumor types, such as brain tumors, liposarcomas, and breast cancers.
  • It often carries multiple oncogenes, which drive tumor growth and contribute to drug resistance.
    • Oncogenes are mutated genes that can trigger cancer and are essential for activating tumor development.

4. Violates Mendel’s Third Law:

  • Mendel’s Law states that genes located on different chromosomes are inherited independently, meaning they are passed on randomly to the next generation.
  • However, ecDNA breaks this rule by keeping genes grouped together and passing them as a cluster during cell division. This helps cancer cells inherit beneficial genes more easily, speeding up tumor growth.
  • Unlike regular chromosomes, which are distributed randomly, ecDNA is passed along as a package.

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