DNA Repair

Summary

DNA repair is a vital cellular process that identifies and corrects DNA damage from both internal and external sources, which can occur up to a million times per cell daily. The script explains how cells detect alterations in the DNA helix and initiate repair through various mechanisms, including nucleotide excision, base excision, mismatch repair, and double-strand repair methods like non-homologous end joining and homologous recombination. It highlights the importance of these processes in preventing diseases such as melanoma and the potential consequences of repair failure, including senescence, apoptosis, and cancer.

Takeaways

• 🧬 DNA repair is a set of processes that identify and correct damage to the DNA molecules in a cell's genome.
• 🔍 Damage to DNA can originate from two sources: endogenous (internal, like normal metabolic activities) and exogenous (external, such as environmental factors).
• 🔢 Human cells may experience up to one million incidents of DNA damage per cell per day, highlighting the constant activity of DNA repair mechanisms.
• 🔍🧬 DNA damage is recognized by alterations in the spatial configuration of the DNA helix, which cells can detect.
• 🛠️ DNA repair mechanisms are categorized into single strand and double strand repair, each with specific methods depending on the type of damage.
• ☀️ UV light exposure can cause pyrimidine dimers, which are repaired by nucleotide excision repair involving specific enzymes and DNA polymerase.
• 🧪 Base excision repair is utilized when damage to a particular DNA base occurs, such as deamination induced by chemicals like nitrates.
• 🔄 Mismatch repair corrects errors that occur during DNA replication and recombination, involving mis-paired nucleotides.
• 🧬🔗 Double strand repair mechanisms include non-homologous end joining, microhomology-mediated end joining, and homologous recombination, each dealing with breaks in both DNA strands.
• 🧬🔧 Homologous recombination uses a sister chromatid or homologous chromosome as a template for repair, involving enzymatic machinery similar to chromosomal crossover during myosis.
• 🛑 Cells with accumulated DNA damage or ineffective repair mechanisms may enter senescence, undergo apoptosis, or lead to unregulated cell division potentially forming tumors.

Q & A

What is DNA repair?

DNA repair is a set of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome.

What are the two main sources of DNA damage mentioned in the script?

The two main sources of DNA damage are endogenous (internal) sources from normal metabolic activities within a cell, and exogenous (external) sources from environmental factors.

How many incidences of DNA damage can occur per cell per day?

Together, the two sources of damage can result in as many as one million incidences of DNA damage per cell per day.

How is DNA damage recognized by the cell?

Damage to DNA alters the spatial configuration of the helix, which can be detected by the cell, such as a bulge in the DNA double helix.

What are the two main types of DNA repair mechanisms?

The two main types of DNA repair mechanisms are single strand repair mechanisms and double strand repair mechanisms.

What are the three main types of single strand repair mechanisms?

The three main types of single strand repair mechanisms are nucleotide excision repair, base excision repair, and mismatch repair.

How does nucleotide excision repair work?

Nucleotide excision repair involves specific enzymes called endonucleases cutting out the damaged nucleotides, DNA polymerase replacing the bases, and DNA ligase resealing the gap.

What is the consequence of nucleotide excision repair failure in the context of UV light exposure?

Failure of nucleotide excision repair to fix damage caused by UV light can lead to melanoma, a form of skin cancer.

How does base excision repair address DNA damage?

Base excision repair uses specific glycosylases to recognize and remove the damaged base, followed by endonuclease cutting the phosphodiester backbone, and then DNA polymerase filling the gap and ligase resealing it.

What is mismatch repair and why is it important?

Mismatch repair corrects errors that occur in DNA replication and recombination, leading to mis-paired but not necessarily damaged nucleotides, ensuring the fidelity of genetic information.

What are the three main mechanisms of double-strand repair?

The three main mechanisms of double-strand repair are non-homologous end joining, microhomology-mediated end joining, and homologous recombination.

How does non-homologous end joining differ from other double-strand repair mechanisms?

Non-homologous end joining directly joins the two ends of a break without the need for a homologous template, using a specialized DNA ligase and a co-factor.

What role does homologous recombination play in double-strand repair?

Homologous recombination requires the presence of an identical or nearly-identical sequence to be used as a template for the repair of the break, often using a sister chromatid or a homologous chromosome.

What are the possible outcomes for a cell that has accumulated a large amount of DNA damage or can no longer effectively repair its DNA?

A cell with accumulated DNA damage or ineffective repair mechanisms can enter senescence (a state of dormancy), undergo apoptosis (programmed cell death), or experience unregulated cell division leading to tumor formation and potentially cancer.