1. Mutation and DNA repair

2. As result this change will affect protein function.
A mutation is a change that happens in DNA sequence (A,C,G,T), either due to mistakes when the DNA is copied or as the result of environmental elements for example Smoking, UV light and radiation.
Mutations can occur anywhere from a single (base pair) to a large segment of a chromosome that includes multiple genes.
As result this change will affect protein function.
Mutation can also disturb a normal gene expression and cause disease ( CANCER).
Original SEQ.
Mutated SEQ.

3. Mutations are divided into two classes:
Heredity mutation:( also known a germ line mutation) inherited form a parent and exist in every cell in the body.
Acquired (somatic mutation): happen during person’s life and just found in certain cells.
Each cell relies on thousands of proteins to do their jobs in the right places at the right times. Sometimes, gene mutations stop one or more of these proteins from function properly. When a mutation changes a protein that has a critical role in the body, it can disrupt normal development or cause a medical condition. A condition caused by mutations in one or more genes is called a genetic disorder.
In some cases gene mutations are so severe, which prevent the fetus from surviving until birth.

4. https://youtu.be/5bLEDd-PSTQ
Apart from the usual Met codon, mammalian cells can also START translation with the amino acid leucine the CUG codon ( very rare). Mitochondrial genomes use AUA and AUU in humans.

5. Silent mutation. Missense mutation. Nonsense mutation.
Gene mutations have a vary effects on human health based on where mutation occurs as well as gene function, so mutations types are:
Silent mutation.
Missense mutation.
Nonsense mutation.
Frameshift mutation

6. Silent mutation: not changing an amino acid, but in some cases can still have a phenotypic effect, e.g., by speeding up or slowing down protein synthesis, or by affecting splicing.
This is a 96-well plate containing the bacteria expressing different versions of the GFP gene.
Credit: Josh Plotkin and the University of Pennsylvania

7. Missense mutation: change in one DNA base pair, leads to changing in amino acid, so another protein may be made.

8. Nonsense mutation: change in DNA base pair, so, changed DNA send a signal to deter making a protein, that leads to produce shorter protein (not function at all or function improperly).

9. Frameshift mutation: Addition or loss of DNA bases changes a gene's reading frame. A reading frame composed of groups of 3 bases that each code for one amino acid. Protein is nonfunctional

10. DNA proofreading and repair
DNA proofreading: Correct the errors during DNA replication process.
DNA mismatch repair: Fix the miss-paired bases after DNA replication process.
DNA damage repair: detect, then correct the damage DNA.

11. Proof reading
DNA polymerases are the enzymes that build DNA in cells. During DNA replication, most DNA polymerases do a process called proofreading, which is based on checking their work with each base that they add.
If the DNA polymerase detects a wrong base paired (nucleotide) has been added, it will remove and replace the nucleotide right away (Exonuclease), before continuing with DNA synthesis.

12. Mismatch repair:
Proofreading(DNA polymerase) fixes most of DNA, BUT they may be some not being fixed. So, mismatch repair occurs right after DNA replication process, fixing the incorrect base pair via removing incorrect base pair and replace it with the right one. Mismatch repair is also able to detect and correct small insertions and deletions.

13. How mismatch repair process works
1- Protein complex recognizes and binds to the wrong base pair.
2-complex CUT the DNA near to the mismatch paired and more enzymes involved to remove the wrong base pair as well as the surrounding bases.
3- DNA polymerase involve to replace the missing bases with correct ones and then ligate (seal) DNA strand by enzyme called DNA ligase.

14. Direct reversal: directly fixes by enzymes in the cell.
DNA damage repair:
Direct reversal: directly fixes by enzymes in the cell.
Excision repair: one or a few damaged bases of DNA is often fixed by removal (excision) and replacement of the damaged region.
Double stranded break repair: happens when the entire chromosome divide. Two major ways: non-homologous end joining and homologous recombination.

15. DNA Repair Pathways and Mechanisms
Happy reading
DNA Repair Pathways and Mechanisms
Thomas S. Dexheimer