2.12 DNA Mutagenesis, Repair and Relevant Diseases Flashcards
Any permanent heritable change in the DNA base sequence of an organism
Mutation
Has the potential to change the base sequence of mRNA and the amino acid sequence of proteins
Mutation
Organisms that are the exact same compy
Clone
DNA molecules are cleaved and the fragments are rejoined to give a new combination
Recombination
Recombination results to
Generation of new gene/allele combinations
Generating new genes
Integration of a specific DNA or virus
DNA repair
Purpose of recombination
For mapping of genes on chromosomes
For making transgenic cells and organisms
3 types of mutation
Point Mutation
Frame shift Mutation
Large segment deletion
Replacement of a single base with another single base nucleotide
Point mutation
2 types of point mutation on the level of the DNA
Type I: Transition
Type 2: Transversion
Name the type of point mutation. Cytosine -> Thymine
Transition
Name the type of point mutation. Thymine-> Adenine
Transversion
Point mutations lead to the following effects in proteins
Silent mutation
Missense mutation
Nonsense mutation
New codon codes for the same amino acid
Covered by buffering systems
Silent mutation
In silent mutation, there is usually a base change in ____
third position
True or false
Silent mutation has no effect on protein.
True
New codon codes for a different amino acid
Has variable effects of protein
Missense mutation
Missense mutation is called ____ if the new amino acid is similar to the old in terms of chemical structure
Conservative
On the other hand, missense mutation is considered ___ when the mutation results in a different amino acid with different properties.
Non-conservative
In sicke cell anemia, __ is produced instead of glutamic acid
Valine
New codon is stop codon
Nonsense mutation
Nonsense mutation results in a ___ and __ protein product
Truncated
Non-functional
Deletion or addition of a number of bases not divisible by three
Frame shift mutation
Frame shift mutation results in a truncated and usually non-functional protein product, just like in ___ mutation
Nonsense
Loss of large areas of chromosomes during unequal crossover in meiosis
Leads to loss of function
Large segment deletion
Characterized by intellectual disability, delayed development, small head size, low birth weight and weak muscle tone during infancy
Affected individuals ave distinctive facial features, including widely set eyes, low-set ears, small jaw, and a rounded face
Cri-du-chat
Cri-du-chat is caused by a deletion of the end of the short arm of chromosome __
5
DNA damage is caused by ___ that escaped proofreading.
Mismatched strands
DNA repair occurs in ___ of cell cycle
G2
Nicks the mismatched strand and the mismatched base is removed
Endonuclease
Enzymes that complete the repair after endonuclease nicked the mismatched strand
DNA polymerase I
DNA ligase
Also known as Lynch syndrome
Hereditary Non-polyposis colorectal cancer (HNPCC)
Familial clustering of cancers at several sites
Hereditary non-polyposis colorectal cancer
Hereditary non-polyposis colorectal cancer is due to ___ and ___
Mismatch repair deficiency
Microsatellite instability
Caused by gene mutations and epigenetic alterations (activation of oncogenic pathways and inactivation of tumor suppressor genes)
Colorectal cancer
Thymine dimers exposed to UV light prevents DNA from replicating the DNA strand beyond the dimers
Xeroderma pigmentosum
Damaged DNA due to exposure of UV light by thymine dimers are removed by ___ and the resulting gap is filled by ____
UV-specific endonuclease
DNA polymerase I
Remove abnormal nitrogenous bases by hydrolytically cleaving N-glycosidic bond from the deoxyribose-phosphate backbone
Glycosylases
Makes a nick at the 5’-site of the AP site
AP endonucleases
Types of recombination
Homologous
Site specific
Transposition
Occurs between sequences that are nearly identical
Homologous
Occurs between sequences with a limited stretch of similarity
Site specific
DNA element moves from one site to another
Transposition
Mismatched base pairs that escape the proofreading step are repaired by Mut proteins
Mutation to proteins involved in this is associated with Lynch syndrome
Methyl-directed mismatch repair
Repair mechanism
UV light exposure causes covalent binding of two adjacent pyrimidies
UV light damage repair
Repair mechanism
DNA nitrogen bases altered spontaneously or through deaminating/alkylating compounds
Base excision repair
Repair mechanism
Double-strand breaks caused by high-energy radiation or oxidative free radicals
Double strand break repairs
