Genetics Unit 13: Dna Repair

Front 1

What is the sole methylated base in eukaryotic DNA

Back 1

5-methylcytosine, always precedes a guanine.

Front 2

What are the methylated bases in prokaryoctic DNA

Back 2

N6-Methyladenine and N4-Methylcytosine.

Front 3

Two types of methyltransferases necessary for dna methylation

Back 3

De novo methyltransferase - methylates previously unmodified DNA
Maintenance methyltransferase - ensures that all bases methylated in parental DNA are also methylated in the daughter strands during replication. Recognize hemimethylated regions of DNA and methylate the unmethylated region.

Front 4

ICF immunodeficiency syndrome

Back 4

Caused by mutations in a de novo methyltransferase gene.

Front 5

5-Azacytididne

Back 5

Cytidine base analog. In dividing cells, blocks maintenance methylation. Can lead to gene activation (used to treat Beta thalasemia and a pre-leukemia disorder).

Front 6

How does DNA methylation exert its effect?

Back 6

By binding proteins which specifically bind methylated DNA which can interfere directly with transcription or by recruitment of other regulation genes.

Front 7

Rett Syndrome

Back 7

X-linked progressive neurodevelepmental disorder. One of most common causes of mental retardation in females, fatal to males. 60% of time caused by mutation of a gene encoding methyl-binding protein.

Front 8

Thymine Dimer

Back 8

Ultraviolet sunlight which causes DNA dimerization mutation. Dimerization draws adjacent thiamine residues together, distorting helix. Replication past site is blocked.
2 forms: cyclobutane and 6-4 photoproduct.
Fixed by light and dark (excision) repair.

Front 9

O6-Alkylation of guanine

Back 9

Alkylation (aka O methylation) of guanine leads it to be paired with a thymidine instead of a cytidine. O6-alkylguanine alkyltransferase is an enzyme which corrects this problem by transfering the methyl or ethyl group from the guanine to a cystine residue on the enzyme.

Front 10

Nucleotide excision repair (dark repair)

Back 10

A section of DNA, including the damaged site, are excised. The section is replaced by a DNA polymerase followed by a ligase.

Front 11

Xoderma Pigmentosum

Back 11

Autosomal recessive disease due to the deficiency in one or more enzymes involved in nucleotide excision repair (and therfore uv-photodamage repair). 5000% more likely for skin cancer. Tumors are to sun-expposed areas.

Front 12

Trichothiodystrophy

Back 12

Genetic disease caused by a deficiency in nucleotide excision repair. Causes by dry, sparse, and brittle hair. Can increase photosensitivity and have increased uv sensitivity and mutability.

Front 13

Mismatch repair

Back 13

If a polymerase dosent catch a missmatch itself, the DNA can undergo mismatch repair. Where helical distortions occur due to mismatched bases or single base additions or deletions.
The newly synthesized strand can be recognized (in e.coli) b/c the newly synthed strand has yet to be methylated at distinct points (GATC on the A) indicating its the new one.

Front 14

Transposons

Back 14

Transposable genetic elements which do not have fixed locations in the genome. Present in all cell types. Are targets for recombination. Can also deleterious inversions and deletions.

Front 15

Gene amplification seen in response to methotrexate

Back 15

Gene aplification leads to high levels of gene expression. Can be caused by the creation of extra-chromosomal copies of a gene region called double minute chromosomes or by a gene region being replicated and added to a chromosome in homogeneously staining region.

Front 16

3 diseases caused by the amplification of neucleotide triplet repeats.

Back 16

Fragile X, myotonic dystrophy, and Huntington's disease

Front 17

Light repair

Back 17

Repairs thymine dimers. Uses light as energy source and photolyase as its enzyme to break the thymine-thymine bond.

Front 18

Homologous recombination mech

Back 18

1) Doublr stranded break in DNA
2) Some DNA is removed creating 2 overhangs.
3) Unbroken homologue reaches up and fills one void.
4) Broken overhang fills vacancy in unbroken homologue.
5) DNA polymerase creates DNA where its missing.
6) Separation of chromosomes occurs by an endonuclease which creates nicks, 2 possible outcomes, cross over or no cross over.

Front 19

Mechanisms for anticipation

Back 19

1) Unequal crossing over - In meiotic recombination, unequal crossing over leads one strand with too many repeats and another with too few. This hypoth. is not complete b/c a chromosome with less than normal repeats is never transferred to offspring.
2) Slipage - Occurs during DNA replication. When a polymerase falls off, there is a chance the new daughter strand will unattach at the unfinished end. If it does not re attach, a buckle occurs after polymerase finishes. If this problem was noticed by the cell, mismatch repair will occur. If it kills wrong strand, the extended strand will be used as a template.

Front 20

Hereditary nonpolyposis colorectal cancer (HNPCC)

Back 20

Cancer predisposition syndrome which can lead to colon as well as ovarian, uterian, kidney cancers with tumors before age 50.
Dominantly inherited but needs two hits. Caused by some mutation in genes coding for mismatch repair. This is evident b/c there are lots of "microsatleite DNA" found in the genome of tumors (too many/too few of neulcleotide repeats caused by a slippage error in replication).