DNA Replication and Telomerase Biochemistry 

Overview

DNA replication is the process by which a cell duplicates its DNA before cell division. This process is crucial for the inheritance of genetic information from one generation of cells to the next. The replication of DNA is a complex process involving many enzymes and proteins.

The first step in DNA replication is the separation of the two strands of the DNA molecule. This is achieved by an enzyme called helicase, which unwinds the DNA double helix by breaking the hydrogen bonds between the complementary base pairs. Once the strands are separated, they act as templates for the synthesis of new DNA strands.

The next step is the synthesis of new DNA strands, which is carried out by an enzyme called DNA polymerase. DNA polymerase reads the sequence of the template strand and adds complementary nucleotides to the growing new strand. The nucleotides are added in a specific order dictated by the template strand, following the base-pairing rules (A-T and C-G).

YouTube video

Treatment

  • DNA replication and telomerase biochemistry are not medical conditions but are important topics in molecular biology research.
  • Shortening of telomeres can lead to genomic instability and promote the development of cancer.
  • Telomerase is an enzyme that can add DNA sequence repeats to the ends of chromosomes, thus preventing their shortening and maintaining their stability.
  • Some cancer cells have high levels of telomerase activity, which allows them to continue replicating indefinitely.
  • Research is underway to develop therapies that target telomerase activity in cancer cells, with the aim of inducing telomere shortening and slowing or stopping cancer growth.
  • There are currently no FDA-approved drugs that target telomerase for cancer treatment.
  • Developing such therapies is an active area of research and may hold promise for future cancer treatments.

Studies

  • DNA replication is a complex process that involves many enzymes and proteins working together to ensure the accurate duplication of genetic material.
  • Telomeres are the protective caps at the ends of chromosomes that prevent the loss of genetic information during DNA replication.
  • Telomerase is an enzyme that can add DNA sequence repeats to the ends of chromosomes, thereby preventing telomere shortening and maintaining chromosome stability.
  • Telomerase is not active in most normal human cells, but it is active in some stem cells, germ cells, and cancer cells.
  • The study of telomerase and telomere biology has important implications for aging, cancer, and stem cell research.
  • Telomere shortening has been linked to aging, age-related diseases, and cancer, and understanding telomerase regulation and activity is crucial for developing treatments for these conditions.
  • Research on telomerase and telomeres has led to the development of drugs that target telomerase activity in cancer cells, as well as potential therapies for age-related diseases and conditions.

Function

  • replicate cell genome in a manner that is highly accurate

Process

    • DNA melted to expose single strand to expose origin of replication
    • single stranded binding proteins (SSBs) bind and stabilize melted DNA
    • RNA primer added in 5′ → 3′ direction by primase
    • DNA polymerase adds adds nucleotides in a 5′ → 3′
      • DNA polymerase III in prokaryotes
      • DNA polymerase α and δ in eukaryotes
      • can edit mistakes with a 3′ → 5′ exonuclease activity
      • adds continuously on the leading strand
      • adds discontinuous Okazaki fragments on the lagging strand because it must synthesize in a 5′ → 3′ direction 
    • DNA gyrase (topoisomerase II) breaks the DNA to prevent coiling 
    • RNA primer removed 
      • by RNAase H in eukaryotes and filled by a DNA polymerase
      • by DNA polymerase I in prokaryotes and can fill simultaneously
    • DNA ligase seals the nick between fragments

Difference between prokaryotes eukaryotes

    • prokaryotes
      • single origin of replication
    • eukaryotes
      • multiple origins of replication

Clinical importance

    • antibiotics
      • quinolones, fluoroquinolones block bacterial topoisomerase
        • used to treat aerobic gram negatives in UTIs and gonorrhea
        • e.g. drugs ending in -floxacin
    • cancer chemotherapy
  • etoposide, teniposide block eukaryotic topoisomerase

Check out the USMLE STEP 1 COURSE.