Genetics lecture 4/10: DNA repair mechanisms and Genetic testing

DNA repair mechanisms (7)

1. proofreading
2. mismatch repair
3. base excision repair
4. photo reactive repair
5. nucleotide excision repair
6. non-homologous end joining
7. synthesis-dependent strand annealing

what makes a mistake about 1 in every 100,000 bases?

DNA polymerase 3

DNA poly has what?

proofreading

How does proofreading work?

DNA poly recognizes that it makes a mistake or that there is distortion. Removes wrong base and adds right one

Exonucleus removes what?

removes a nucleotide

Proofreading catches how many mistakes

99% of mistakes

Mismatch repair

base-base mismatches, small insertions, and small deletions that are there after proofreading

What is strand discrimination?

Adenine methylase adds methyl groups to certain adenines during DNA rep. New synthesized strand is temporarily unmethylated

When does mismatch repair occur?

During or right after DNA replication

Base excision repair does what?

correct damaged DNA bases(depurination example) or base-pair mismatch (outside of DNA replication)

base excision repair proteins do what?

recognize the base pair mistake

when can base excision repair occur?

at anytime, not DNA replication exclusive

Photoreactive repairs do what?

uses light to cleave the bonds between thymine dimers

Photoreactive repair is found in what?

bacteria, plants, and some animals (NOT HUMANS)

Nucleotide excision repair does what?

repairs bulky lesions in DNA that distorts the double helix (larger segments)

What are the steps of NER?

1. error detection
2. nucleotide excision
3. nucleotide replacement
4. nucleotide linkage

What is the only mechanism for thymine dimer repair in humans?

Nucleotide excision repair

Are sister chromatids present in G1?

NO!

Sister chromatids are synthesized in what phase?

S phase (DNA replication)

what is non homologous end joinging?

repairs DSB (double-stranded breaks) in G1.

Why is nonhomologous end joining problematic?

because it creates blunt ends before ligating the strands together. ends up in a deletion (hopefully in noncoding part…)

Synthesis-dependent strand annealing does what?

occurs in G2. repairs DSBs during late S or G2 phases of the cell cycle

steps for SDSA (synthesis-dependent strand annealing)

1. 5’ to 3’ resection
2. strand invasion
3. new DNA synthesis
4. strand annealing

no crossing over!

crossing over occurs between….

NONSISTER chromatids

SDSA occurs when?

AFTER dna replication

If DNA repair mechanisms are not working, what can be the result of mutations?

cancer

when to do pre-symptomatic genetic testing

anytime after birth. some states require you to be 18

why do pre-symptomatic genetic testing

to determine if someone is carrying a mutation that will cause disease in the future

how does pre-symptomatic genetic testing work?

DNA sequencing or PCR to determine if someone has a wildtype of mutated alleles

what are two examples of diseases for pre-symptomatic genetic testing?

Huntingtons disease and the BRCA1/BRCA2 mutations

when to get carrier genetic testing?

before conception or during first trimester

why get carrier genetic testing

to determine if they are heterozygous for mutations that cause serious or fatal recessive diseases in children

how does carrier genetic testing work?

detects wild-type or mutant proteins in a blood sample, or DNA analysis (sequencing or PCR)

what are two examples of diseases to detect for in carrier genetic testing?

sickle cell disease, cystic fibrosis