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Biochemistry 2280A
Christopher Brandl

DNA Repair ● To preserve genetic information, the cell must guard against unintended changes in the sequence or structure of DNA, which will be referred to as DNAdamage ● The main types of DNAdamage are mentioned below Copying Mistakes ● Despite the proofreading ability of DNApolymerase, mistakes can still occur and this can possibly lead to a change in the DNAsequence or mutation in daughter DNA Deamination ● The amine group of a nitrogenous base, most commonly cytosine is changed to a carbonyl; occurs spontaneously and may lead to mutation; upon deamination, cytosine is converted to uracil Depurination ● Acid promotes the loss of an entire adenine or guanine base resulting in an abasic site ● The sugar-phosphate backbone remains intact but abasic sites block replication by the normal replicative DNApolymerase ● Honestly, check this in the lecture notes, this doesn’t seem like something we talked about Pyrimidine dimers ● The double bonds in adjacent pyrimidines, most commonly two thymines, react to form a cyclobutane ring; usually caused by UV radiation ● Translesion DNApolymerases are required to replicate DNApast pyrimidine dimers, but are more error-prone than normal replicative DNApolymerases, increasing risk of mutation Other base modifications ● Ionizing radiation such as X-rays or gamma rays, causes a variety of modifications to all four bases ● Some chemicals called mutagens react with DNAbases, leading to sequence changes Strand breaks ● Ionizing radiation or mechanical stress can break the sugar phosphate backbone, either of one strand (single strand break) or both strands (double strand break) ● Neither the normal replicative DNApolymerases nor translesion polymerases can synthesize DNApast a break in the template ● Double stranded breaks can cause chromosomal abnormalities or result in cell death DNARepair Systems ● Asingle alteration in a DNAmolecule, if left unrepaired, could interfere with the replication process and may cause the death of the cell ● DNAdamage can also cause mutations which can alter the sequence of expressed proteins and impair their function ● The following are DNArepair systems Proofreading during DNAreplication ● See topic 20 Mismatch repair ● Mismatch repair enzymes fix mistakes made by DNApolymerase that escaped correction by proofreading with a success rate of 99% ● After repair machinery has detected a site of mismatch, it must determine which strand is the newly synthesized strand; does this by scanning DNAin both direction
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