Molecular Biology Chapter 5 DNA Damage Repair and Mutation

Chapter 5 DNA Damage Repair and Mutation

first quarter

Damage: such as bases, methylation

Mutation: A change in base pairing

• Most DNA damage can be repaired;
• Other biomacromolecules are degraded after damage;
• reason:
  • On the one hand, the copy number of the DNA molecule inside the cell is low: it must be repaired
  • On the other hand, the structure of DNA dictates its ease of repair: it can be repaired

Section 2 Types of DNA Damage

1 Factors that cause DNA damage

• Internal factors:
  • Instability of the DNA structure itself;
  • Base mismatches in DNA replication;
  • Oxygen free radicals (reactive oxygen species, Ros);
• envirnmental factor:
  • Chemical factors - various chemical mutagens, such as aflatoxins, alkylating agents, etc.
  • Physical factors - ultraviolet radiation and ionizing radiation (x-rays and v-rays), etc.

2 Types of DNA damage

• Base damage:

  • base loss
  • base conversion
  • base modification
  • base crosslinking
  • base mismatch

• 

• DNA strand damage:

  • chain break
  • Cross-linking of DNA strands
  • Cross-links between DNA and proteins

3 DNA damage repair mechanism

• DNA is the only biomolecule that can be purposefully repaired; other biomolecules are degraded or replaced after damage.
• Even among organisms with very small genomes, more than 100
• Genes are involved in various DNA repair mechanisms.
  Many tumors (probably most tumors) are associated, at least in part, with defects in DNA repair machinery.

3.1 Direct fix

• Feature: Direct reversal of damaged DNA
  • As old as old

3.2 Excision repair

• multi-step;

• Can repair most DNA damage:

  • Cut off the old and put in the new

• general steps

  • Recognize
  • Remove
  • Resynthesize
  • Reconnect

3.3 Double-strand break repair

• A DNA double-strand break is a serious injury;
• Cells have two main mechanisms to repair DNA double-strand breaks;
  • Homologous recombination: higher accuracy: yeast;
  • Non-homologous end joining: low accuracy; mammalian; (low accuracy, tends to cause mutations)

3.4 Recombination Repair

• Also known as post-replication repair;
• Rely on homologous recombination mechanism;
• After replication, the damage remains, awaiting true DNA damage repair;

3.5 Synthesis across

• Random addition of nucleotides (correct or incorrect) to the daughter strand at the damaged site by a special DNA POl;
• There are more than 30 kinds of DNApol involved in spanning synthesis in the human body, and these enzymes are generally very low in progress (one or several nucleotides)
  and have no proofreading function;
• error-prone bypass