(MTM) MCB 2.7 - DNA Damage Mutation Repair

cytosine to uracil

in spontaneous dna damage, deamination is a loss of an amino group on the base, usually ___ to ___

thymine

-5’-CG-3’ sequences have a tendency to mutate to 5’-TG-3’

-MUTATION HOTSPOTS

when 5’ methylcytosine (DNA methylation) is deaminated, it becomes ___

depurination

in spontaneous dna damage, ___is a loss of an entire purine and creates an AP site

methyl

methylguanine

in induced DNA damage, alkylating agents add ___ groups to bases. ____ mis-pairs with T (instead of cytosine) resulting in replication errors

insertions, deletions, and frameshifts

in induced DNA damage, intercalating agents (planar molecule) slide between bases, pushing them apart resulting in ___,___, and ____

free radicals

in induced DNA damage, ionizing radiation such as x rays and gamma rays generate ___ that introduce double strand breaks

pyrimidine dimers

covalent

in induced DNA damage, UV rays causes ____ which introduces ___bonds on the same strand

phosphodiester

in induced DNA damage, ROS cleaves ____ bonds which breaks single and double stranded DNA

mutagenesis

The process by which a stable change in the genetic information of an organism occurs

null mutation

what type of mutation results in a complete loss of function or a completely nonfunctional protein is produced

partial loss of function mutation

A mutation that reduces but does not completely eliminate the protein activity

loss of function

Complete or partial decrease in protein activity

gain of function

Increase in protein activity, or creation of a new activity

dominant negative mutations

type of mutation that result in mutated proteins that interfere or block the function of wild type protein

Dominant Negative > Null > Partial loss of function

order these from most severe to least severe clinical presentation:

null

partial loss

dominant negative

Genome > Chromosomal > Gene

order from most common type of level mutation to least:

genome

gene

chromosome

silent mutation

-nucleotide has changed by the codon for the protein is the same

mutation that does not alter the amino acid sequence of a protein

Nonsense mutation

mutation that introduces stop codon

null

nonsense mutation in eukaryotes result are considered __ due to mRNA degradation

conservative missense

a mutation where the mutated amino acid has similar properties to the original amino acid

nonconservative missense

a mutation where the mutated amino acid is different than the original 

non-stop mutations

a mutation that replaces a stop codon with an amino acid coding codon resulting in longer proteins

null mutations

splice site mutations result in insertions or deletions in the coding sequence that results in a frameshift. they introduce premature termination codons and result in mRNA degradation and are usually ___ mutations

5’ end

GU

splice donor is at the ___ end of the intron and the bases are __

3’ end

AG

splice acceptor is at the ___ end of the intron and the bases are __

acceptor

intron retention is when a splice ___ is lost and an intron is retained in the mRNA

acceptor

exon skipping is when a splice ___ is lost and an exon is removed in the mRNA

cryptic splice site

a new splice acceptor or donor site, causing abnormal mRNA splicing. This is caused by a single base mutation

frameshift

-Null mutation 

-premature termination codon (PTC)

a mutation that the number of bases inserted or deleted is NOT a multiple of 3

short tandem repeat

___ sequences (microsatellites /VNTRs) are prone to expansion or contraction as they are passed from parent to offspring

expansions

in replication: Backward slippage in slipped-strand mispairing results in ___

Contractions

in replication Forward slippage in slipped-strand mispairing results in ___

mismatch repair

-corrects slippages in tandem repeats

corrects replication errors (wrong bases or small insertions/deletions) by excising the newly made DNA segment and replacing it

detecting differential hemi-methylation of adenine in the old (correct) strand

-Mut factor

mismatch repair in prokaryotes can distinguish the old (correct) strand from the incorrect (new) by ___

Mut factor

in mismatch repair of prokaryotes, what factor recognizes the hemi-methylation of the old (correct) strand and nicks the new strand

MSH and MLH

in mismatch repair of eukaryotes, what repair proteins recognize the single strand DNA break of the new strand

MSH and MLH

expansions

lynch syndrome is due to a mutation in which repair proteins which causes microsatellite ____ that were supposed to be corrected

colorectal cancer

Lynch syndrome or HNPCC has an increased risk for ____ cancer

bulky

-example:

pyrimidine dimers (UV rays)

bulky adducts

nucleotide excision repair (NER) corrects ____ damage to a (single or double) strand of DNA 

XPB and XPD helicase

in NER, which enzymes remove the bulky damage?

UV-induced pyrimidine dimers

xeroderma pigmentosum (XP) is caused by a mutation in the XP genes which results in the inability to remove ___

Base excision repair (BER)

repairs specific bases that were deaminated, alkylated, depurinated, and oxidized

non-homologous end joining (NHEJ)

is an error-prone mechanism to repair double stranded DNA breaks

-the ends are directly joined

homologous recombination

repairs double-strand breaks accurately by using a sister chromatid as a template through strand invasion and DNA synthesis.

BRCA1 and BRCA2

in homologous recombination, what genes are involved in dsDNA break repair?

BRCA1 and BRCA2

breast cancer is due to a mutation and loss of function of which genes?

NBM

in Nijmegen Breakage Syndrome, the ___ gene that encodes for nibrin is mutated which prevents the repair of dsDNA

autosomal recessive

Chromosome Instability Syndromes are all what type of mode of inheritance?

nondisjunction

most common cause of aneuploidy is ___

unequal crossing over

most common cause of chromosomal rearrangement is ____

ATM

-cell does pause for repair (fails checkpoint)

Ataxia Telangiectasia has a defect in the ____ protein that detects dsDNA. Therefore in homologous recombination, it is unable to repair the dsDNA

BLM

bloom syndrome has a mutated ___ genes that causes increased sister chromatid exchange

WRN

Werner syndrome has a mutated ___ gene that shortens telomeres

FA

fanconi anemia has a mutated ____ genes which causes increased interstrand crosslinks