The document discusses mismatch repair (MMR), a critical DNA repair mechanism that fixes errors during DNA processing to maintain genomic stability and cellular homeostasis. It highlights the historical context of MMR's discovery by Tomas Lindahl, Paul Modrich, and Aziz Sancar, who received the Nobel Prize in Chemistry in 2015, and outlines the roles of various proteins involved in both prokaryotic and eukaryotic MMR systems. Additionally, the MMR pathway is emphasized for its importance in promoting apoptosis, genomic stability, and antibody diversity.

1. MISMATCH REPAIR
LOGESWARAN KA
P20BIT1013
I MSC BIOTECHNOLOGY
PERIYAR UNIVERSITY

2. DNA REPAIR
Set Of Processes Where A Cell Detects And Nullify Damages Occurred
In DNA.
Very Important Mechanism Since Its Failure Leads To Development Of
Severe Diseases.
Discovery  “Tomas Lindahl, Paul Modrich And Aziz Sancar”.
They Received “Nobel Prize In Chemistry” In The Year “2015”.
Their Research Focused On “Molecular Mechanisms Of DNA Repair
Processes”.

3. DNA DAMAGE CAUSES
DNA Damages Are Caused By “Exposure To Several Endogenous And
Exogenous Agents”.
“Errors Occurred During DNA Processing Reactions” Also Causes
Damages In The DNA.
Endogenous Agents  Reactive Oxygen, Nitrogen (Metabolites)
Exogenous Agents  UV, Dioxin (Chemical And Physical Agents)
DNA Processing Reactions  Replication, Recombination And Other
Biological Processes.

4. MISMATCH REPAIR
“Mismatch Repair (MMR)” Recognizes And Replaces The Wrong Bases
Arised Due To “Unwanted Insertion And Deletion” During The DNA
Processing Interactions.
Important Role In “Maintenance Of Genomic Stability” And “Cellular
Homeostasis”.
There Are “Two” Types.
Prokaryotic MMR.
Eukaryotic MMR.

5. MMR COMPLEX STRUCTURE

6. PROKARYOTIC MMR
Mut S  Important Protein Of MMR  Initiates MMR Pathway By Recognizing
Non-specific Interactions  2 Functional Domains  DNA Binding Domain And
ATPase Domain.
Mut L  Mediator Protein B/W Mut S And Other Proteins  Interacts With Mut S
And Initiates Endonuclease Activity Of Mut H Protein  Acts As Recruiter Of
UVrD Protein.
Mut H  Type II Restriction Endonuclease  It Removes Mismatch DNAAt
Hemimethylated GATC Sites  Mut H Capacity For Mismatch Removal Is
Stimulated By Mut S + Mut L + ATP Complex.
UVrD  DNA Helicase II Enzyme  It Unwinds The DNAAt Nick Point Made By
Mut H  The Nick Point Is The Entry Point For Single Stranded DNA Binding
Protein And UVrD  UVrD Takeup At Nickpoint Is Mediated By Protein-Protein
Interactions With Mut L.

7. EUKARYOTIC MMR
MSH  MSH6 Protein  Similar To Mut S  Mut Sa (Mismatch Recognition)
And Mut Sb (Mismatch Repair). i.e. Insertion Deletion Loops (IDL).
MLH  Similar To Mut L  Responsible For Formation Of Heterodimer  Three
Types Of Mut L Are Mostly Studied.
1. Mut La  Supports Repair Initiated By Mut S Protein.
2. Mut Lb  Functions Not Found.
3. Mut Lg  Metabolic Recombination.
Accessory Proteins  Responsible For Proper Functioning Of MMR  Helps In
Recognition, Binding And Removal Of DNA Mismatch. i.e. Proliferating Cell
Nuclear Antigen (PCNA) And Exonuclease I (EXO I).

8. MMR PATHWAY

9. BIOLOGICAL IMPORTANCE
It Promotes DNA Damage Induced Cell Cycle Arrest And Apoptosis.
It Promotes Genomic Stability.
It Increases “Antibody Diversity” By Promoting Immunoglobulin Class
Switching And Somatic Hypermutation.
It Promotes Trinucleotide Repeats (TNR) Expression [Under Research].
It Promotes Homologous Recombination.
It Promotes Interstrand Crosslink Repair Mechanisms.

10. REFERENCES
1) https://www.nature.com/articles/cr2007115
2) http://mcb.berkeley.edu/courses/mcb110/ALBER/13.14
.repair.pdf
3) https://www.slideshare.net/mprasadnaidu/dna-repair-
final
4) https://www.creative-diagnostics.com/mismatch-repair-
pathway.htm

11. THANKS FOR LEARNING