DNA Methylation Review

Concept of DNA Methylation

  • DNA methylation is a crucial and high-yield topic in genetics that contributes significantly to understanding genetic mechanisms and their implications in health and disease.

    • Importance of detailed understanding for exams and lectures.

    • Encouragement to engage with educational content and support the channel.

Overview of DNA

  • DNA serves as the genetic code in living organisms.

    • Locations of DNA:

    • In eukaryotic cells, DNA is found in the nuclei.

    • In prokaryotic cells, DNA resides in the cytoplasm.

    • Mitochondria also contain DNA, referred to as mitochondrial DNA, but it is not located in the nucleus; however, this subject will be discussed in future lectures.

  • Structure of DNA:

    • DNA is a polymer composed of nucleotides.

Composition of Nucleotides

  • Nucleotides contain three key components:

    1. Sugar Backbone

    • Ribose-based sugar: Nucleotides can be either ribonucleotides (in RNA) or deoxyribonucleotides (in DNA).

      • Key distinction:

        • Deoxyribose (in DNA): does not have an OH group on the second carbon.

        • Ribonucleotide (in RNA): has an OH group on the second carbon.

    1. Nitrogenous Base

    • These bases allow for the pairing of DNA strands through hydrogen bonding.

    • Types of bases discussed:

      • Adenine

      • Cytosine

      • Guanine

      • Thymine

    1. Phosphate Group

    • The phosphate is essential for distinguishing between nucleotides and nucleosides.

    • Nucleosides: do not have a bound phosphate.

Introduction to DNA Methylation

  • DNA methylation is a mechanism crucial for regulating gene expression and maintaining genetic integrity.

    • It serves several functions, including:

    • Regulation of DNA transcription and translation.

    • Conservation of genetic processes to prevent mutations associated with cancer.

    • High fidelity in transcription and translation is necessary to minimize errors that can lead to cancer.

Mechanism of DNA Methylation

  • Methylation process:

    • A methyl group ($-CH_3$) binds to the nitrogenous base of DNA, particularly affected bases like cytosine.

    • The binding often occurs in regions known as CpG islands.

CpG Islands

  • Definition:

    • Regions within DNA containing a high frequency of cytosine and guanine base pairs.

    • These areas are significant due to the strong bonding (three hydrogen bonds) between cytosine and guanine, making these regions stable and less prone to breakage.

  • Methylation occurs in these CpG islands, affecting both strands of DNA.

Effects of DNA Methylation

  • Inactivation of DNA Transcription:

    • Increase in DNA methylation leads to a decrease in DNA transcription.

    • This relationship is significant as it introduces essential concepts relating to epigenetics, indicating gene expression can be modulated not only by the genetic code but also through methylation patterns.

  • Clinical Implication:

    • Around 70-75% of human DNA is reportedly methylated, which serves as a defense mechanism.

    • Unmethylated DNA triggers immune responses, as it is often interpreted as foreign or infected.

    • Cancer Biology:

    • Highly unmethylated regions in cancer cells can result in their detection by the immune system, leading to apoptosis or immune attack on these cells.

    • Cancer cells often replicate uncontrolled, leading to more unmethylated DNA that elicits immune responses.

Immune Recognition of Unmethylated DNA

  • The body distinguishes between human DNA and foreign DNA:

    • Human DNA (70-75% methylated) versus bacterial DNA (typically unmethylated).

    • This distinction plays a role in autoimmune responses and immune defense mechanisms, especially against pathogens.

Importance of Methylation

  • As a defense mechanism against infections:

    • Bacterial DNA is mainly unmethylated, making it easier for the immune system to detect and respond to infections.

    • Bacteriophage viruses target bacteria, and bacterial DNA with methylation is less susceptible to their attack.

  • In essence, unmethylated DNA in human cells is seen as potentially harmful, prompting immune responses regardless of whether it originates from cancer or an infection.

Summary and Conclusion

  • Key takeaway:

    • High levels of DNA methylation result in decreased transcription of DNA into RNA, which ultimately affects protein synthesis.

  • Understanding DNA methylation is not only important for academic purposes but also for appreciating mechanisms underpinning cellular regulation and disease processes.