14 June 2024
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Scientists from Tokyo Metropolitan University have been studying the DNA repair pathway by homologous recombination, where the RecA protein repairs breaks in double-stranded DNA by incorporating a dangling single-strand end into intact double strands, and repairing the break based on the undamaged sequence.

DNA Repair Pathway: Unraveling the Steps for Genetic Healing



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Our DNA, the blueprint of life, is constantly under attack from various environmental and internal factors that can cause breaks in its double-stranded structure. These breaks, if left unrepaired, can lead to cell death or mutations that may contribute to diseases like cancer. Fortunately, our cells have an intricate repair mechanism called homologous recombination (HR) that works tirelessly to mend these DNA breaks.

The Mechanism of DNA Repair Pathway

HR is a fundamental process found in all living organisms, from bacteria to humans. It involves a series of steps that work together to accurately repair double-strand breaks in DNA.

1. Resection: Exposing the Broken Ends

The first step in HR is resection, where the ends of the broken DNA strands are trimmed, exposing single-stranded overhangs. This process creates a “dangling” single-strand end that serves as a starting point for repair.

2. RecA Protein: The Matchmaker of DNA Repair Pathway

Once the single-stranded ends are exposed, a protein called RecA (or its equivalent in other organisms) comes into play. RecA acts as a matchmaker, binding to the single-stranded end and searching for an intact double-stranded DNA molecule that contains the same genetic sequence.

3. Strand Invasion: Integrating the Single Strand

When RecA finds the matching sequence on the intact DNA molecule, it promotes strand invasion, where the single-stranded end is integrated into the double helix. This process is crucial for aligning the broken DNA strand with its undamaged counterpart, allowing for accurate repair.

4. DNA Polymerase: Filling the Gaps

Once the single strand is integrated, DNA polymerase, another key player in DNA repair, takes over. It uses the intact DNA strand as a template to fill in the gaps and synthesize new DNA, extending the single strand and restoring the continuity of the DNA molecule.

5. Ligation: Sealing the Break

Finally, an enzyme called ligase steps in to seal the remaining gap between the newly synthesized DNA and the existing DNA strand. This final step completes the repair process, restoring the DNA molecule to its original state.

The Importance of DNA Repair Pathway

HR plays a vital role in maintaining the integrity of our genetic material. It ensures accurate repair of double-strand breaks, preventing potentially harmful mutations and safeguarding the stability of our genome. Additionally, HR facilitates genetic diversity by enabling the exchange of genetic information during sexual reproduction.

DNA Repair Pathway and Cancer

Defects in HR can have far-reaching consequences. Mutations in genes involved in HR, such as BRCA1 and BRCA2, have been linked to an increased risk of breast and ovarian cancer. These genes are responsible for the proper functioning of HR, and their malfunction can lead to accumulation of DNA damage and an increased likelihood of cancer development.

Conclusion: Advancing Cancer Research

The study of DNA repair mechanisms like HR holds immense promise for advancing cancer research. By understanding the intricate details of HR, scientists can uncover new targets for cancer therapies and develop strategies to prevent or treat cancer more effectively.

FAQ’s

1. What is Homologous Recombination (HR)?

HR is a fundamental DNA repair mechanism found in all living organisms. It involves a series of steps that work together to accurately repair double-strand breaks in DNA, preventing cell death and mutations that may contribute to diseases like cancer.

2. What are the steps involved in HR?

HR involves five main steps:

  • Resection: Exposing the broken ends of DNA.
  • RecA Protein: Binding to the single-stranded end and searching for an intact DNA molecule with the same genetic sequence.
  • Strand Invasion: Integrating the single strand into the double helix.
  • DNA Polymerase: Filling in the gaps and synthesizing new DNA.
  • Ligation: Sealing the remaining gap between the newly synthesized DNA and the existing DNA strand.

3. Why is HR important?

HR plays a crucial role in maintaining the integrity of our genetic material. It ensures accurate repair of double-strand breaks, preventing potentially harmful mutations and safeguarding the stability of our genome. Additionally, HR facilitates genetic diversity by enabling the exchange of genetic information during sexual reproduction.

4. How are defects in HR linked to cancer?

Mutations in genes involved in HR, such as BRCA1 and BRCA2, can lead to an increased risk of breast and ovarian cancer. These genes are responsible for the proper functioning of HR, and their malfunction can result in the accumulation of DNA damage and an increased likelihood of cancer development.

5. How can the study of DNA repair mechanisms like HR help advance cancer research?

Understanding the intricate details of HR can uncover new targets for cancer therapies. By studying HR, scientists can develop strategies to prevent or treat cancer more effectively. Additionally, HR research can shed light on the mechanisms underlying genetic diversity and the evolution of new species.

Links to additional Resources:

https://www.tmu.ac.jp/en/ https://www.nature.com/ https://www.science.org/

Related Wikipedia Articles

Topics: DNA repair pathway, RecA protein, Homologous recombination

DNA repair
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encodes its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in tens of thousands of individual molecular lesions per...
Read more: DNA repair

RecA
RecA is a 38 kilodalton protein essential for the repair and maintenance of DNA. A RecA structural and functional homolog has been found in every species in which one has been seriously sought and serves as an archetype for this class of homologous DNA repair proteins. The homologous protein is...
Read more: RecA

Homologous recombination
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may be also RNA in viruses). Homologous recombination is widely used by cells to accurately repair harmful...
Read more: Homologous recombination

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