Mutations, DNA Repair, Replication Errors

What is a point mutation?

-Change in a single base pair

-Transition or transversion

What is a transition?

-Purine↔purine or pyrimidine↔pyrimidine

-A → G

What is a transversion?

-Purine↔pyrimidine

-A → T

What is a synonymous mutation?

-Codon changes but amino acid stays the same

-Silent mutation at wobble position

What is a missense mutation?

-Codon change → different amino acid

-Sickle cell anemia (Glu→Val)

What is a conservative missense mutation?

-Amino acid replaced with similar one

-Leu→Ile

What is a non‑conservative missense mutation?

-Amino acid replaced with very different one

-Hydrophobic→charged

What is a nonsense mutation?

-Codon becomes STOP

-Truncated protein

What is a frameshift mutation?

-Insertion/deletion shifts reading frame

-Early STOP codon

What happens when mutations occur in coding regions?

-Protein structure/function changes

-Loss‑of‑function or gain‑of‑function

What happens when mutations occur in regulatory regions?

-Gene expression changes

-Promoter mutation reduces transcription

What does photolyase repair?

-UV‑induced pyrimidine dimers

-Uses visible light to reverse damage

What does nucleotide excision repair fix?

-Bulky lesions

-UvrA/B/C remove thymine dimers

What does mismatch repair fix?

-Replication errors

-MutH cuts unmethylated daughter strand

How does mismatch repair identify the correct strand?

-Parent strand is methylated

-Dam methylase marks GATC sites

What is proofreading?

-3’→5’ exonuclease activity of DNA polymerase

-Removes incorrect nucleotides

What is replication slippage?

-DNA polymerase slips on repeats → expansion

-Fragile X CGG repeat expansion

What is anticipation?

-Disease severity increases in successive generations

-Fragile X, Huntington’s

What is a somatic mutation?

-Occurs in non‑gamete cells; not inherited

-Cancer mutations

What is a germline mutation?

-Occurs in gamete lineage; inherited

-PKU mutation

What is a lethal recessive allele?

-Causes death only in homozygotes

-Tay‑Sachs

Why do lethal recessive alleles persist?

-Hidden in heterozygotes

-Carriers unaffected

What is transcription‑coupled repair?

-RNA Pol II stalls at lesion → recruits repair enzymes

-Preferential repair of active genes

What is SOS repair?

-Error‑prone repair activated in severe damage

-Bypass polymerases insert random bases

What is base excision repair?

-Fixes small, non‑bulky lesions

-Uracil removal by glycosylase

What is double‑strand break repair?

-Fixes breaks via NHEJ or homologous recombination

-BRCA1/2 involved in HR

What is NHEJ?

-Non‑homologous end joining; error‑prone

-Small insertions/deletions

What is homologous recombination repair?

-Uses sister chromatid as template; error‑free

-Occurs in S/G2 phase

What causes thymine dimers?

-UV radiation

-Adjacent thymines covalently bond

What is a mutagen?

-Agent that increases mutation rate

-UV, X‑rays, chemicals