DNA Repair and Recombination Flashcards
What is Xeroderma Pigmentosum?
Disorder caused by a defect in the DNA repair pathway nucleotide-excision repair
Uv Sens., excessive freckling, skin cancers, corneal ulcerations
What are three types of repair mechanisms?
- Repair involving excision of lesion followed by replacement
- Direct repair
- Double-stranded break repair
What is the mechanism of mismatch repair?
Endonuclease nicks the strand, followed by exonuclease degradation.
DNA Pol III and DNA ligase fill in the lost DNA
What is the cause of HNPCC or Lynch syndrome?
Mutations in the mismatch repair mechanism.
What are Mut proteins?
Proteins responsible for recognizing the mismatch and identifying the methylated parent strand.
How are pyrimidine dimers formed?
UV light causes adjacent pyrimidines to dimerize (mostly thymines)
interfere with replication and transcirption
What fixes pyrimidine dimers?
Photoreactivation or nucleotide-excision repair
What is nucleotide excision repair?
Repairs damage resulting in large distortions of the DNA double helix (e.g. pyrimidine dimers)
What is excinuclease?
UV-specific endonuclease
Defect in this enzyme is the cause for Xeroderma Pigmentosum
Why does DNA contain thymine and not uracil?
Uracil is readily produced by chemical degradation of cytosine, so having thymine makes detection and repair more efficient
What is depurination?
Loss of base leaving just the phosphate and sugar.
Creates an abasic site
Higher rate for purines
What is the mechanism of Ricin?
Acts by depurination of adenine in rRNA
What is Base-excision repair?
Repairs altered bases resulting fro spontaneous changes and environmental insults
Primarily responsible for removing small, non-helix-distorting base lesions
What is spontaneous deamination?
Spontaneous deamination of a base
What is the function of Deoxyribose phosphate lyase?
Removes the base free phosphate residue so that the insult can be repaired
What is MBD4?
glycosylase employed in an initial step of base excision repair
binds to fully methyated CpG sites and their altered DNA bases
What is Direct Repair?
A specific enzyme (methyltransferase) repairs the damage, rather than using a set of enzymes
Does not involve DNA polymerase
What causes double stranded breaks?
High-energy radiation
Oxidative free radicals
What are the two mechanisms of double stranded break repair?
Nonhomologous end-joining repair (more error prone of the two)
Homologous recombination repair
What are BRCA1 and BRCA2?
Genes implicated in breast and ovarian cancer
Involved in homologous recombination repair
What is DNA recombination?
The rearrangement or exchange of genetic information between two DNA molecules or between two different parts of the same DNA molecule
What is the difference between legitimate and illegitimate DNA recombination?
Legitimate - fidelity is preserved, no information lost (crossing over)
Illegitimate - fidelity is not preserved
What is a Holliday Junction?
Junction between recombined portions of two homologous chromosomes
What is the result of unequal crossing over?
insertion or duplication in one strand, and deletion in the other
What contributes to unequal crossing over?
Short repetitive sequences
Similar regions in different genes
These sequences confuse annealing
What are Alu sequences?
Transposable elements within the genome that can act as disease markers
What diseases are linked with Alu insertions?
Breast Cancer Ewing's sarcoma Familial hypercholesterolemia Hemophilia Neurofibromatosis
