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DNA Replication and Repair

Introduction​

DNA replication and repair are fundamental processes in molecular biology that play crucial roles in maintaining genetic integrity and ensuring proper cell function. This chapter will explore both processes in detail, providing insights into their mechanisms, importance, and relevance to various biological systems.

Key Concepts​

  • DNA structure and replication machinery
  • Types of DNA damage
  • Mechanisms of DNA repair
  • Impact of DNA replication errors on cellular function

DNA Structure and Replication Machinery​

Before diving into DNA replication and repair, it's essential to understand the basic structure of DNA and the proteins involved in its replication.

DNA Structure​

DNA (Deoxyribonucleic acid) is a double-stranded helix composed of nucleotides. Each nucleotide consists of a sugar molecule called deoxyribose, a phosphate group, and one of four nitrogenous bases:

  1. Adenine (A)
  2. Guanine (G)
  3. Cytosine (C)
  4. Thymine (T)

The sequence of these bases determines the genetic information encoded in DNA.

Replication Machinery​

The process of DNA replication requires several key enzymes and proteins:

  1. Helicase: Unwinds the double helix
  2. Primase: Adds RNA primers
  3. DNA polymerase: Synthesizes new DNA strands
  4. Ligase: Seals gaps between Okazaki fragments

DNA Replication Process​

DNA replication occurs during the S phase of mitosis and meiosis. It involves unwinding the double helix, synthesizing new complementary strands, and sealing the gaps.

Step 1: Initiation​

  • The replication fork forms where the double helix is unwound
  • An RNA primer is added to the template strand

Step 2: Elongation​

  • DNA polymerase reads the template strand and matches incoming nucleotides
  • New DNA strands grow in the 5' to 3' direction

Step 3: Termination​

  • When the entire genome is replicated, the replication fork collapses
  • RNA primers are removed and replaced with DNA

DNA Damage and Repair​

DNA damage can occur due to environmental factors, errors during replication, or other cellular processes. There are two main types of DNA damage: single-strand breaks and double-strand breaks.

Single-Strand Breaks​

Single-strand breaks occur when only one strand of the DNA double helix is damaged. These can be repaired through:

  1. Base excision repair
  2. Nucleotide excision repair

Double-Strand Breaks​

Double-strand breaks are more severe and can lead to chromosomal instability. They are repaired through:

  1. Non-homologous end joining (NHEJ)
  2. Homologous recombination repair (HRR)

Mechanisms of DNA Repair​

Let's explore the mechanisms of DNA repair in detail:

Base Excision Repair (BER)​

Base excision repair is the primary pathway for repairing damage to individual bases in DNA. It involves several steps:

  1. Recognition of damaged base
  2. Removal of damaged base
  3. Filling of gap with nucleotides
  4. Proofreading and correction

Key enzymes involved in BER include:

  • DNA glycosylases
  • AP endonuclease
  • DNA polymerase beta
  • DNA ligase

Nucleotide Excision Repair (NER)​

Nucleotide excision repair is responsible for removing larger DNA lesions, typically those that distort the double helix structure. The process involves:

  1. Recognition of DNA damage
  2. Incision on either side of the lesion
  3. Removal of the damaged segment
  4. Synthesis of new DNA strand
  5. Ligation of the remaining nick

Key enzymes involved in NER include:

  • XPC protein complex
  • UvrABC enzyme complex
  • DNA polymerase eta
  • DNA ligase

Non-Homologous End Joining (NHEJ)​

Non-homologous end joining is one of the main pathways for repairing double-strand breaks. It involves:

  1. Recognition of broken ends
  2. Processing of broken ends
  3. Direct ligation of the broken ends

Key enzymes involved in NHEJ include:

  • Ku70/Ku80 heterodimer
  • DNA-dependent protein kinase (DNA-PK)
  • Ligase IV

Homologous Recombination Repair (HRR)​

Homologous recombination repair is another pathway for repairing double-strand breaks. It involves:

  1. Recognition of broken ends
  2. Search for homologous sequences
  3. Strand invasion
  4. Extension of invading strand
  5. Resolution of recombinant products

Key enzymes involved in HRR include:

  • BRCA1 and BRCA2 proteins
  • RAD51 protein
  • RAD52 protein

Impact of DNA Replication Errors on Cellular Function​

Errors during DNA replication can lead to various consequences:

  1. Point mutations: Single-base substitutions that may alter gene function
  2. Frameshift mutations: Insertions or deletions that change the reading frame of genes
  3. Chromosomal abnormalities: Large-scale changes in chromosome structure

These errors can result in genetic disorders, cancer development, or other cellular dysfunctions.

Conclusion​

Understanding DNA replication and repair is crucial for grasping fundamental biological processes and their implications for human health and disease. This chapter has covered the essential concepts, mechanisms, and importance of these processes, providing a solid foundation for further exploration in molecular biology.