1. Their Role and Regulation
DNA Polymerases:
Their Role and Regulation
January 31, 2018

2. DNA Replication

3. The DNA Polymerases Family A Family B Family X Family Y
Pol γ Pol α Pol β Pol η
Pol υ Pol δ Pol λ Pol ι
Pol θ Pol ε Pol μ Pol κ
Pol ζ Pol σ Rev 1

4. The Role of DNA Polymerases

5. Why Study DNA Polymerases?
Biochemistry
Genetic Control Elements
Evolution
DNA Polymerases
Regulation
Genomic Stability
Disease and Cancer

6. Xeroderma Pigmentosum - Variant
-Autosomal recessive disease resulting from Pol η mutations
-Inability to bypass T-T dimers
-Patients have an increased sensitivity to sunlight and a higher incidence of skin cancer

7. Translesion Synthesis Reaction
INSERTION
EXTENSION
Pol-DNA14
Pol-DNA15
koff
DNA13
Pol-DNA16
dNTP
Pol
DNA14
DNA15
Kin
Kex
Pol-DNA14
Pol-DNA15
koff
DNA13
Pol-DNA16
dNTP
Pol
DNA14
DNA15
Kin
Kex
dNTP
dNTP
dNTP
DNA13
Pol-DNA14
Pol-DNA15
Pol-DNA16
Kin
Kex
koff
koff
Pol
Pol
DNA14
DNA15
DISSOCIATION
Gestl and Eckert, 2005

8. Translesion Synthesis Model
Pol δ
Pol η
Pol δ
Pol η

9. Model for XP-V Phenotype
+ Pol ?
+ Pol 
Polymerases  and ? work in tandem to complete error-free TLS
In the absence of pol , another polymerase performs error-prone TLS

10. Journal Article Control of spontaneous and damageinduced
mutagenesis by SUMO and
ubiquitin conjugation
Philipp Stelter & Helle D. Ulrich

11. Zebrafish Model System
-Production of hundreds of transparent eggs biweekly
-ex utero development of
embryos
-Generation time of 3 months
-Relatively inexpensive
-Vertebrate organism
-Can develop tumors
Synthesis
Protein Folding
Covalent Modification
Binding of other
cofactors or proteins
Day 3

12. Post-Translational Modifications
Covalent modification of proteins by enzymes necessary to elicit a specific biological response
-Phosphorylation
-Methylation
-ADP-Ribose
-Acetylation
-Ubiquitination
-SUMOlation

19. Sumo

20. Sumo -Small protein molecule, ~100 AA
-4 SUMO molecules found in mammals, SUMO1, SUMO2, SUMO3, SUMO4
-Conjugation is similar to Ubiquitination

21. Sumoylation

22. Comparison of Sumo
and Ubiquitin