DNA replication: origins, fork machinery, leading/lagging strand, telomere maintenance.
Replication
DNA replication
Semiconservative duplication of the genome (Meselson-Stahl 1958), catalysed by DNA polymerases at replication forks initiated at origins.…
Replication fork
Moving Y-shaped junction at which parental duplex is unwound and both daughter strands synthesised. Houses helicase, primase, polymerases,…
Origin of replication
Locus where replication initiates. Bacteria have single oriC (245 bp AT-rich); eukaryotes use multiple origins licensed by ORC + Cdc6 +…
DNA polymerase
5′→3′ template-directed polymerase with nucleotidyl-transferase mechanism. Replicative polymerases (bacterial Pol III; eukaryotic α/δ/ε)…
Okazaki fragment
Discontinuous 1-2 kb (bacteria) / 100-200 nt (eukaryotes) DNA fragments synthesised on the lagging strand, each primed by a short RNA,…
Helicase
ATP-dependent motor that unwinds duplex DNA ahead of the replication fork. Bacteria: DnaB (5′→3′). Eukaryotes: CMG complex…
Telomere
Repetitive DNA-protein cap at eukaryotic chromosome ends (TTAGGG in vertebrates) that buffers end-replication loss. Shortens with each…
Telomerase
Ribonucleoprotein reverse transcriptase (TERT catalytic subunit + TERC RNA template) that extends 3′ telomere overhangs. Active in stem…
Replication timing programme
Genome replicates in a deterministic spatiotemporal order — euchromatin early, heterochromatin late. Associated with gene expression,…
Replication stress
Stalled/collapsed replication forks from nucleotide shortage, DNA damage, R-loops. ATR-Chk1 response. Key cancer hallmark; targetable by…
Leading/lagging-strand DNA-replication framework
DNA polymerases extend only 5'→3'; consequence at a replication fork: leading strand is synthesised continuously toward the fork; lagging…
Telomere end-replication framework
End-replication problem (Olovnikov 1971; Hayflick 1965 limit): linear chromosome ends (telomeres) shorten by ~50-200 bp per replication…
Watson-Crick (1953)
Watson-Crick 1953 (Nobel 1962) DNA structure; semi-conservative replication; foundation of molecular biology.
Meselson-Stahl (1958)
Meselson-Stahl 1958 semi-conservative replication confirmed via 15N CsCl-density-gradient; 'most beautiful experiment in biology'.
Origins (Jacob-Brenner-Cuzin 1963)
Jacob-Brenner-Cuzin 1963 replicon-model; modern E coli oriC + ARS yeast + ORC eukaryote; 50000 origins per human nucleus.
Okazaki fragments (1968)
R Okazaki 1968 lagging-strand fragments; modern replication-fork dynamics; pol-delta + pol-epsilon + Lig-1.
Licensing (Blow-Laskey 1986)
Blow-Laskey 1986 replication-licensing; modern MCM helicase + Cdc6/Cdt1; ensures once-per-cycle replication.
Telomere (Blackburn-Greider 1985)
Blackburn-Greider-Szostak Nobel 2009 telomere/telomerase; modern aging + cancer-targets imetelstat.
Replicon (Jacob-Brenner-Cuzin 1963)
Jacob-Brenner-Cuzin 1963 replicon-model; modern eukaryotic 50000+ origins per nucleus; ORC + MCM + Cdc6/Cdt1.
DNA pol classes
Modern eukaryotic Pol-alpha/delta/epsilon + prokaryotic Pol-I/II/III + lesion-bypass Y-family; modern fidelity 10^-9 per bp.
Topoisomerase (Wang 1971)
J Wang 1971 + Liu 1979 topoisomerase I/II; modern fluoroquinolone + etoposide chemotherapy targets.
Replisome (Costa 2014)
Costa 2014 + Yeeles 2015 reconstituted replisome; modern in-vitro DNA replication + cryo-EM structures.
PCNA (Bravo 1989)
Bravo 1989 PCNA + clamp-loader RFC; modern eukaryotic processivity 10^4 bp + leading-strand fidelity.
Replication checkpoint (Tercero-Diffley 2001)
Tercero-Diffley 2001 ATR-Chk1 replication-checkpoint; modern fork-protection + replication-stress-response cancer-therapy.