DNA Repair and Mutations

Flashcards about DNA Repair and Mutations

What serves as a template to correct damaged genomic DNA?

An undamaged DNA strand

What is the correlation between mutation accumulation and eukaryotic cells?

Linked to Cancer

What is the occurrence ratio of lesions and mutations?

Thousands of lesions/day but only 1/1,000 become a mutation

What does a lesion become if it is unrepaired?

Mutation

What are the types of mutations?

Substitutions (point mutations), deletions, additions

What is a silent mutation?

Has ~no effect on gene function or affects a nonessential region of the DNA

How do mismatches arise?

From occasional incorporation of incorrect nucleotides (DNA replication errors)

How do abnormal bases arise?

From spontaneous deamination, chemical alkylation, or exposure to free radicals

How do pyrimidine dimers form?

When DNA is exposed to UV light

How do backbone lesions occur?

From exposure to ionizing radiation and free radicals

In E. coli, what enzymes/proteins are involved in Mismatch repair?

Dam methylase, MutH, MutL, MutS proteins, DNA helicase II, SSB, DNA polymerase III, Exonuclease I, Exonuclease VII, RecJ nuclease, Exonuclease X, DNA ligase

In E. coli, what enzymes/proteins are involved in Base-excision repair?

DNA glycosylases, AP endonucleases, DNA polymerase I, DNA ligase

In E. coli, what enzymes/proteins are involved in Nucleotide-excision repair?

ABC excinuclease, DNA polymerase I, DNA ligase

In E. coli, what enzymes/proteins are involved in Direct repair of Pyrimidine dimers?

DNA photolyases

In E. coli, what enzymes/proteins are involved in Direct repair of O6-Methylguanine?

O6-Methylguanine-DNA methyltransferase

In E. coli, what enzymes/proteins are involved in Direct repair of 1-Methylguanine and 3-methylcytosine?

AlkB protein

How do Mismatch repair enzymes know which strand is the correct one?

In E. coli, the parent strand is methylated

What type of methylation occurs in E. coli?

Dam methylase inserts CH3 at adenines in the GATC sequence

How long does the daughter strand remain unmethylated?

For a short period of time

What is cleaved in the methyl-directed mismatch repair system?

The unmethylated strand

What proteins recognize methylated GATC?

MutL and MutS proteins

What binds to the MutL-MutS-DNA complex?

MutH

What does MutH do to the nonmethylated DNA strand?

Cleaves it on the 5’-side of the G

What unwinds and degrades DNA 3’à5’?

Helicase II (UvrD helicase), SSB, and exonucleases

What replaces and seals the removed sequence?

DNA Pol III and DNA ligase

What do DNA glycosylases do?

Recognize specific lesions and cleave N-glycosyl bond between sugar and base, creating an apurinic/apyrimidinic (AP) site

What does Uracil glycosylase do?

Removes uracil from DNA

What do AP endonucleases do?

Cut the DNA backbone around the AP site and remove DNA

What synthesizes new DNA during base excision repair?

DNA Pol I

What do photolyases use to repair pyrimidine dimers?

Light energy

What repairs methylated guanine?

O6-methylguanine-DNA methyltransferase

What demethylates 1-methyladenine and 3-methylcytosine?

AlkB

What are the repair mechanisms when there is no undamaged DNA to use as a template?

Recombination, nonhomologous end joining (NHEJ), and error-prone translesion synthesis (TLS)