But the story doesn’t end there. Once an Okazaki fragment is complete, the RNA primer is a vestigial error. Enter and FEN1 (flap endonuclease 1), the editors. They remove the RNA and fill the gap with DNA. Finally, DNA ligase I seals the nick, forging a continuous sugar-phosphate backbone. Page 217 emphasizes that failure of this cleanup leads to genomic instability—a hallmark of cancer. Scene 3: The Proofreaders and the Backup Hidden in the margins of page 217 is a crucial note on fidelity. DNA polymerase δ has a proofreading subunit (3′→5′ exonuclease activity). It double-checks each nucleotide just added. If a mismatch is found, the polymerase reverses, excises the error, and tries again. This reduces the error rate from 1 in 10⁵ to 1 in 10⁷.
But what about damage already present on the template strand—like a base altered by oxidation or UV light? Page 217 introduces (TLS) as a desperate measure. Special polymerases (η, ι, κ) bypass the lesion, albeit with low accuracy. This is a controlled gamble: better to introduce a mutation than to leave the replication fork collapsed, which would break the chromosome. Scene 4: The Telomere Coda The final paragraph on page 217 turns to a problem unique to linear chromosomes: end replication . After the last RNA primer on the lagging strand is removed, a short gap remains at the 3′ end of the template. Without intervention, chromosomes would shorten by 50–200 bp per division. genetica molecular humana strachan pdf 217
Scene 1: The Fork in the Road On page 217, we find ourselves at a critical moment in the life of a human cell: the replication fork. The double helix has just been pried apart by helicase enzymes, revealing two single strands of DNA. One strand, the leading strand , is oriented favorably for continuous copying. The other, the lagging strand , must be copied in short, disjointed fragments (Okazaki fragments). Page 217 explains how the cell solves this asymmetry. But the story doesn’t end there
