DNA Repair Mechanisms

Mismatch Repair (MMR)

Damage addressed: mismatches from DNA replication errors, such as incorporation of a non-complementary base. Used after DNA replication before mitosis. Key players: MutS, MutL, MutH in bacteria; MSH and MLH in humans.

Base Excision Repair (BER)

Damage addressed: small, non-helix-distorting base lesions caused by deamination, oxidation, or alkylation. Used anytime during the cell cycle. Key players: DNA glycosylase, AP endonuclease (APE1), DNA polymerase, DNA ligase.

Nucleotide Excision Repair (NER)

Damage addressed: bulky, helix-distorting lesions, such as UV-induced pyrimidine dimers. Used anytime during the cell cycle. Key players: XPC, XPA–XPG, and TFIIH complex.

Homologous Directed Repair (HDR)

Damage addressed: double-strand breaks. Preferentially used during S and G2 when a sister chromatid is available as a template. Key player: RAD51. Generally high-fidelity because it uses a homologous template.

Non-Homologous End Joining (NHEJ)

Damage addressed: double-strand breaks. Used anytime during the cell cycle, especially G1. Directly joins broken DNA ends without a homologous template, making it more error-prone than HDR. Key players: Ku70/80 and DNA-PKcs.

Direct Damage Reversal

Damage is directly reversed rather than removing and replacing DNA. Examples: MGMT repairs O6-methylguanine; photolyase reverses UV-induced pyrimidine dimers in organisms that possess it (not humans). Can occur anytime during the cell cycle.

Translesion Synthesis (TLS)

Damage addressed: bulky DNA lesions that stall replication forks. Used primarily during DNA replication. Specialized DNA polymerases bypass the lesion. Examples: Pol V in bacteria; Pol η, Pol ι, and Pol κ in eukaryotes.

RNA Polymerase I

Synthesizes 5.8S, 18S, and 28S rRNA

RNA Polymerase II

Synthesizes mRNA, miRNA, and lncRNA

RNA Polymerase III

Synthesizes tRNA and 5S rRNA

Which RNA polymerase synthesizes mRNA?

RNA Polymerase II

Which RNA polymerase synthesizes miRNA?

RNA Polymerase II

Which RNA polymerase synthesizes lncRNA?

RNA Polymerase II

Which RNA polymerase synthesizes tRNA?

RNA Polymerase III

Which RNA polymerase synthesizes 5.8S, 18S, and 28S rRNA?

RNA Polymerase I

Which RNA polymerase synthesizes 5S rRNA?

RNA Polymerase III

Which RNA polymerases synthesize snRNA and scRNA?

RNA Polymerases II and III

Don’t Be Fooled, Exams Hurt!!!

Initiation of Transcription in Eukaryotic Cells

TFIID

Binds to promoter (TBP recognizes TATA region)

TFIIB

Binds and positions RNA Pol II relative to promoter so transcription begins @ +1 site

TFIIF

TFIIF brings RNA Pol II and stabilizes interaction w/ promoter & transcription factors

TFIIE

Pre-initiation complex is assembled!!

TFIIH

Opens DNA w/ Helicase activity & Phosphorylates CTD of RNA Pol II