1. 2. a.

Mutation is heritable alterations in genetic materials of organisms. Sources: inaccuracy in DNA synthesis or by chemical damage to genetic materials Types: Base substitution: one base is replaced by another base Insertion: one or more bases are inserted into the DNA sequence Deletion: one or more bases are deleted from the DNA sequence Inversion: a segment of DNA is inverted, but remains at the same overall location Duplication: a segment of DNA is duplicated. The second copy usually remains at the same location as the original Translocation: a segment of DNA is transfer from its original location to another position either on the same DNA molecule or on the different DNA molecule Natures: Transition: Pyr to Pyr and Pur to Pur Transverse: Pyr to Pur and vice versa Base substitution Point mutation: at a nucleotide Replication errors and repair: Replication errors: By proofreading exonuclease DNA mismatch repair system removes errors that escape Proofreading MutS scans the DNA and detects the mismatch MutL activates MutH, an enzyme that cause a nick on a strand near the site of mismatch A specific helicase (UrvD) unwinds the DNA, and the exonuclease progressively digests the mismatch region The gap is then filled by DNA polymerase and sealed with DNA ligase. In E. coli, the parent stand is identified by methylation Dam methylase convert A in GATC into Methyladenine (hemi-methylated) The unmethylated chain will be checked for errors Exonuclease removes the error chains and DNA polymerase will fulfill DNA again. In eukaryotes: by MSH + MSL and PMS. No MutH and no methylation so use MSH interacting with sliding clamp and recruit the mismatch base pairs.

3. a. b. c.

DNA damage: Depurination: A or G will be lost from the DNA Deamination: loss of an amino group from C to produce U Alkylation: methyl or ethyl groups are transferred into active sites of base or phosphate backbones. d. Oxidation: oxoG = oxidation of G e. Thymine dimer:

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UV lights make the formation of cyclo-butane rings between adjacent T Cause DNA Pol stop DNA synthesis. Base analogs: Bromouracil pairs with A or G Repair of DNA damage: Enzymes DNA photolyase captures UV and uses it to break the bonds between T in T dimer. Methyltransferase removes the methyl group from the guanine residue by transfering it to one of its own Cys residues. - An enzyme called glycosylase recognizes and removes the damaged base by hydrolyzing the glycosidic bond. - Glycosylase release the base from the DNA backbone to leave an AP site (apurinic or apyrimidic site) - AP endonuclease and exonuclease cut the DNA backbone at the 5 and 3 position of the AP site - The resulting gap is filled by DNA polimerase I - DNA glycosylase are lesion- specific and the cells have multiple DNA glycosylase with different specificities. A total 8 different DNA glycosylase have been identified in human cells. + 2 UrvA and 1 UrvB scan the DNA to find distortion + UrvB melts around the distortion, releasing UrvA + UrvC forms a complex with UrvB and creates a nick on 5 3 of the lesion + UrvD unwinds and cut the error chain + DNA Pol and ligase fulfill and join the DNA

Number Repair 1 Photoreactivation cleaves Thymine dimer 2 Direct reversal of methylated base 3 Base excision repair: OxoG:A repair

Nucleotide excision repair

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