Base Excision vs. Nucleotide Excision

Attribute	Base Excision	Nucleotide Excision
Definition	Removal of a single damaged base from DNA	Removal of a segment of DNA containing multiple damaged bases
Enzymes involved	DNA glycosylase, AP endonuclease, DNA polymerase, DNA ligase	UvrA, UvrB, UvrC, UvrD, DNA polymerase, DNA ligase
Recognition of damage	Specific recognition of damaged base by DNA glycosylase	Recognition of distortions in DNA structure caused by damage
Size of excised segment	Single damaged base	Multiple bases (around 12-13 nucleotides)
Types of damage repaired	Specific types of base damage (e.g. uracil, 8-oxoguanine)	Bulky lesions, pyrimidine dimers, other distortions

Introduction

Base excision repair (BER) and nucleotide excision repair (NER) are two important mechanisms that cells use to repair damaged DNA. Both processes are crucial for maintaining genomic stability and preventing mutations that can lead to diseases such as cancer. While both BER and NER are involved in DNA repair, they differ in their mechanisms, the types of DNA damage they repair, and the enzymes involved in the process.

Mechanism

Base excision repair is a pathway that repairs damaged DNA by removing and replacing individual damaged bases. It is primarily involved in repairing small, non-helix-distorting lesions such as oxidized or alkylated bases. The process begins with a DNA glycosylase enzyme that recognizes and removes the damaged base, leaving an apurinic/apyrimidinic (AP) site. The AP site is then cleaved by an AP endonuclease, and the gap is filled in by a DNA polymerase and sealed by a DNA ligase.

Nucleotide excision repair, on the other hand, is a pathway that repairs bulky DNA lesions that distort the DNA helix, such as UV-induced pyrimidine dimers. NER involves the recognition and removal of a stretch of nucleotides containing the damaged base. The process is initiated by a complex of proteins that recognize the lesion and create an incision on either side of the damaged site. The damaged DNA segment is then removed, and the gap is filled in by a DNA polymerase and sealed by a DNA ligase.

Types of DNA Damage

Base excision repair is primarily involved in repairing small, non-helix-distorting lesions that result from oxidative damage, alkylation, and deamination. These types of damage can lead to the formation of apurinic/apyrimidinic sites, which are recognized and repaired by the BER pathway. Examples of DNA glycosylases involved in BER include uracil DNA glycosylase (UNG) and 8-oxoguanine DNA glycosylase (OGG1).

Nucleotide excision repair, on the other hand, is primarily involved in repairing bulky DNA lesions that distort the DNA helix, such as UV-induced pyrimidine dimers and chemical adducts. These types of damage can lead to significant distortions in the DNA structure, which are recognized and repaired by the NER pathway. Examples of proteins involved in NER include XPC, XPA, and XPG.

Enzymes Involved

Base excision repair involves a variety of enzymes that work together to recognize, remove, and replace damaged bases in the DNA. These enzymes include DNA glycosylases, AP endonucleases, DNA polymerases, and DNA ligases. Each enzyme plays a specific role in the BER pathway, ensuring that the damaged base is accurately recognized and repaired.

Nucleotide excision repair also involves a complex of proteins that work together to recognize, remove, and replace damaged DNA segments. These proteins include XPC, which recognizes the lesion, XPA, which verifies the damage, and XPG and XPF, which make incisions on either side of the lesion. DNA polymerases and ligases are then recruited to fill in the gap and seal the repaired DNA.

Conclusion

In conclusion, base excision repair and nucleotide excision repair are two important mechanisms that cells use to repair damaged DNA. While both pathways are involved in DNA repair, they differ in their mechanisms, the types of DNA damage they repair, and the enzymes involved in the process. Understanding the differences between BER and NER is crucial for understanding how cells maintain genomic stability and prevent mutations that can lead to diseases such as cancer.