Colon cancer-associated mutator DNA polymerase δ variant causes expansion of dNTP pools increasing its own infidelity Flashcards Preview

Biochemistry 431 > Colon cancer-associated mutator DNA polymerase δ variant causes expansion of dNTP pools increasing its own infidelity > Flashcards

Flashcards in Colon cancer-associated mutator DNA polymerase δ variant causes expansion of dNTP pools increasing its own infidelity Deck (13):
1

Which DNA polymerases are implicated in hereditary colorectal cancer?

DNA polymerases delta and episilon.

2

How does polys-r696W become so mutagenic?

causes s-phase checkpoint-dependent expansion of dNTP pools. Results from errors in nucleotide selectivity defect with activation of the signaling pathway that elevates dNTP pools.

3

DNA polymerase delta

pol3; Lagging strand synthesis

4

DNA polymerase epsilon

pol2; Leading strand polymerase.

5

Who introduced the concept of a mutator phenotype leading to cancer?

Lawrence Loeb

6

Dun1 effector Kinase

plays a role in the regulation of dNTP pools and the transcriptional response to DNA damage.

7

What enzyme precisely regulates dNTP pools during the cell cycle?

Ribonucleotide reductase (RNR)

8

What causes higher levels of dNTP pools?

When cell damage occurs, Mec1, Rad53, and Dun1 levels increase causing higher levels of RNR activity.

9

Why is an increased amount of dNTPs harmful?

pool expansion following DNA damage is accompanied by increased error rate. Leads to mutagensis.

10

How exactly do polymerase 2/3 lead to mutagenesis?

pol2 or 3 mutant and Dun1 interact to increase dNTP levels

11

sm1 and crt1

repressors of RNR

12

Which polymerase is more error prone?

pol3 R696W

13

Poly3-R696W hypothesis

Pol3-R696W is incapable of correcting polyd-R696W errors by the proofreading activity of pold and or MMR. It is found that when poly3-R696w interacts with genes that also have mutations (MMR or other repair mechanisms), mutation rates are synergistic.

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