Dna repair mechanism, Study notes of Genetics

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Role of enzyme in DNA

Proofreading

DNA Repair mechanism

PROOFREADING

During DNA replication most DNA polymerases “ check their work” with each base that they add This process is called proofreading. If the polymerase detects that a wrong (incorrectly paired) nucleotide has been added, it will remove and replace the nucleotide Proofreading by DNA polymerase and exonucleolytic proofreading are two common mechanisms Proofreading occur either during replication or after the completion of replication.

The wrong base has a low binding affinity, polymerase undergoes conformational changes and correct it Sometimes polymerase even can’t recognize and correct the wrong base pairing then exonuclease (which is a domain of polymerase) identifies these weak bindings and helps to correct them The exonuclease activity of the polymerase helps to break the phosphodiester bond and removes the wrong one DNA polymerase adds the right nucleotide

It allows DNA polymerase to recognize and remove the incorrect nucleotide added to the 3' end Also allows DNA polymerase to back up a few nucleotide Increases the accuracy of DNA replication

5'-3' exonuclease activity of DNA polymerase is also involved in

proofreading, but to a lesser extend Removal of nucleotides from the 5' end

DNA polymerase I in bacteria DNA polymerase δ in eukaryotes Removal of RNA primers during DNA replication Responsible for filling the gaps left behind after primer removal

MutS and MutL do conformational changes to give further signals and recruit other proteins and enzymes and prevent packaging in this region MutH binds at hemimethylated sites , being activated only upon contact by mutL dimer which binds to Muts-DNA complex Act as mediator between MutS& Mut L Mut S, Mut L & Mut H are rrequired for recognition of the mutation & to create nick in the strand

DNA Repair DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1 million individual molecular lesions per day Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes DNA repair process is constantly active as it responds to damage in the DNA structure

Reversal of damage In some cases, a cell can fix DNA damage simply by reversing the chemical reaction that caused it "DNA damage" may involves an extra group of atoms getting attached to DNA through a chemical reaction Eg ;Guanine (G) can undergo a reaction that attaches a methyl group to an oxygen atom in the base

The methyl-bearing guanine, if not fixed, will pair with thymine (T) rather than cytosine (C) during DNA replication There is an enzyme that can remove the methyl group, reversing the reaction and returning the normal state

Base excision repair Base excision repair is a mechanism used to detect and remove certain types of damaged bases A group of enzymes called glycosylases play a key role in base excision repair Each glycosylase detects and removes a specific kind of damaged base For example, a chemical reaction called deamination can convert a cytosine base into uracil During DNA replication, uracil will pair with adenine rather than guanine an Incorrected cytosine-to-uracil change can lead to mutation

Glycosylase from the base excision repair pathway detects and removes deaminated cytosine

The result in the formation of an apyridiminic or apurinic site

(generally called an AP site) in DNA

These sites are repaired by AP endonuclease, which cleaves adjacent to the AP site The remaining deoxyribose moiety is then removed, and the resulting single-base gap is filled by DNA polymerase and ligase