Zero Tolerance: DNA Proofreading and Repair

If UV light strikes DNA and causes adjacent thymines to bond (forming a dimer), then the structure of the double helix is distorted. If the cell uses Nucleotide Excision Repair to cut out and replace this distorted section, then the repair is successful.

If a mutation is in a skin cell (somatic), then it only affects the individual. If a mutation in a sperm or egg cell (germ-line) is not fixed, then every cell in the offspring's body will contain that error, potentially harming the whole population.

If the DNA damage is too severe to be fixed, then the cell's "guardian" proteins (like p53) will stop the cell cycle. If the damage cannot be repaired, then these proteins trigger apoptosis to prevent the cell from becoming cancerous.

If cytosine turns into uracil, then the DNA sequence will be read incorrectly during the next round of replication. If the cell uses repair pathways to identify and switch the uracil back to cytosine, then genetic stability is maintained.

If an enzyme has 5' to 3' exonuclease activity, then it can "chew" up a strand ahead of it while building a new one. If DNA Polymerase I uses this to replace primers or damaged segments, then it is a vital part of the repair process.

If an individual lacks the enzymes needed to repair UV-induced thymine dimers, then they will be hypersensitive to sunlight. If this inherited defect is called Xeroderma Pigmentosum, then it is a direct consequence of a failed NER pathway.

If mutations happened too frequently, then every generation would be overwhelmed by genetic defects. If repair systems keep the mutation rate extremely low but not zero, then life can maintain its integrity while still allowing for slow evolutionary change.

If DNA polymerase makes an initial mistake every 100,000 bases, then the error rate is 1 in 10^5. If additional repair mechanisms act after synthesis, then the final error rate drops to nearly 1 in 10^9 or 1 in 10^10.

If a substance can physically break DNA or chemically alter its bases, then it is a mutagen. While radiation and toxic chemicals are known to damage DNA, pure water does not typically cause mutations.

If the DNA polymerase fails to catch a mismatch during synthesis, then a specialized group of proteins scans the new DNA. If these proteins find and fix the "bulge" caused by the mismatch right after replication, then the error rate is significantly reduced.

If a mismatched nucleotide is added to the growing strand, then the enzyme's shape changes and blocks further synthesis. If the enzyme is DNA Polymerase, then it will use its internal exonuclease activity to remove the error and try again.

If an error in base pairing is not caught by polymerase or subsequent mismatch repair, then it becomes a permanent part of the genome. If a change is permanent and inherited, then it is defined as a mutation.

If the enzyme adds nucleotides in the 5' to 3' direction and detects an error at the very end of the strand, then it must move backward to remove it. If moving backward means going from the new end toward the start, then the activity is 3' to 5' exonuclease.

If the MMR system detects a misalignment in the double helix, then it can recognize "loops" formed by extra bases. If it can fix these loops, then it is capable of repairing small insertions or deletions as well as single base mismatches.

If a mismatch is found, then the cell must decide which base is "wrong." If the cell adds methyl groups to the parent strand but has not yet added them to the new daughter strand, then the unmethylated strand is identified as the one containing the error.

If a repair pathway results in a new segment of DNA being built, then there will be a gap where the new piece meets the old piece. If DNA ligase forms the covalent bond to close that gap, then it serves as the final sealer of the repair.

If NER requires cutting the backbone, filling the gap, and sealing the strand, then it must use a nuclease to cut, a polymerase to fill, and a ligase to seal. Ribosomes are for protein synthesis, so they are not involved in this DNA repair.

If UV light causes two thymines on the same strand to link together, then they form a bulky structure that stops the replication fork. If this specific two-part structure is formed, then it is called a thymine dimer.

If a base like cytosine is damaged or converted into uracil, then it must be removed without breaking the whole strand initially. If DNA glycosylase recognizes and flips out the specific damaged base, then the first step of BER is complete.

If mutations accumulate in genes that control growth or cell death, then cancer can develop. If repair enzymes are missing from birth, then syndromes or premature aging may occur; however, the common cold is caused by a virus.