Biochemical Basis of DNA Repair

Introduction

DNA repair is a fundamental process that ensures the stability of the genetic material in living cells. It is essential for maintaining the integrity of the genome and preventing mutations that can lead to diseases such as cancer. The biochemical basis of DNA repair involves a complex network of pathways and mechanisms that detect and correct various types of DNA damage.

Types of DNA Damage

DNA can be damaged by a variety of factors, including exposure to ultraviolet (UV) radiation, chemicals, and reactive oxygen species. The most common types of DNA damage include single-strand breaks, double-strand breaks, base modifications, and crosslinks. These lesions can interfere with DNA replication and transcription, leading to mutations if left unrepaired.

DNA Repair Pathways

There are several major DNA repair pathways in cells, each specialized for repairing specific types of DNA damage. The base excision repair (BER) pathway repairs single-base lesions, such as oxidized or alkylated bases. The nucleotide excision repair (NER) pathway removes bulky lesions caused by UV radiation and chemical carcinogens. The mismatch repair (MMR) pathway corrects errors that occur during DNA replication, while the homologous recombination (HR) and non-homologous end joining (NHEJ) pathways repair double-strand breaks.

Mechanisms of DNA Repair

The biochemical basis of DNA repair involves a series of coordinated steps that recognize, excise, and replace damaged DNA. In the BER pathway, a DNA glycosylase recognizes and removes the damaged base, leaving an abasic site that is cleaved by an AP endonuclease. The DNA polymerase then fills in the gap, and a ligase seals the nick. In the NER pathway, a complex of proteins recognizes and excises the damaged DNA segment, and the gap is filled by a DNA polymerase and ligase. In the HR pathway, a homologous DNA sequence is used as a template to repair double-strand breaks, while the NHEJ pathway directly ligates the broken ends.