DNA Replication: Clinical Correlations

Question 1

Nucleoside analogues: Herpesviruses

Answer 1

• Herpesviruses cause cold sores + genital infections
• Acyclovir (Zovirax) is a guanosine analogue that inhibits the viral DNA polymerase

Question 2

Nucleoside analogues + SARS-Cov2

Answer 2

• Remdesivir and Molnupiravir used from treatment of COVID
• SARS-CoV2 is an RNA virus that encodes for RNA-dependent RNA polymerase (RdRp) which they target
• Prodrugs - converted to nucleotide in cell

Question 3

Reverse Transcriptases in HIV-1

Answer 3

• HIV codes its own DNA polymerase called reverse transcriptase (can use RNA or DNA as a template)
• Synthesises DNA from RNA then uses newly made DNA is used as template to form double strand
• Requires 3’-OH group + doesn’t have a 3’-5’ exonuclease activity

Question 4

Nucleoside analogues & HIV-1

Answer 4

• Azidothymidine (AZT) and 2’3’-dideoxycytidine : lack 3’-OH so stop replication when incorporated into a growing chain

Question 5

DNA replication - Cancer Treatments

Answer 5

• Chemotherapies protocols may be inhibitors of nucleotids metabolism + are used to stop nucleotide biosynthesis
• Fluorouracil block synthesis of thymidine monophosphate

Question 6

X-linked intellectual disability (XLID)

Answer 6

Mutations in over 140 genes including POLA1 gene - codes for catalytic subunit of primase

• Can cause: intellectual disability, short stature, hypogonadism, variable congenital malformations

Question 7

Biotechnology & Bioinformatics

Answer 7

Polymerase chain reaction is DNA replication in a test tube + used for
- determination of gene/genome sequence
- analysis of minute quantities of DNA
- Rapid gene cloning