Exam 4: Mutations and DNA replication/repair Flashcards
Depurination
bond between purine base and deoxyribose spontaneously hydrolyzes
Deamination
Most common is conversion of cytosine to uracil
Pyrimidine dimers
UV light causes dimerization of adjacent thymine bases on same DNA strand
Somatic mutation
affects only cell where mutation occurred
Germline mutation
mutation will be passed to offspring
Gene mutations
variations in nucleotide sequence - affect only one gene
Chromosomal mutations
rearrangements, deletions, or duplications of chromosomal regions
Genomic mutations
addition or loss of chromosomes
Mutations impacting chromatin
changes in methylation of DNA or in modification of histone proteins
Point mutations
exchange of one nucleotide for another
Silent mutation
mutation does not result in change in amino acid sequence
missense mutation
change in sequence results in change in amino acid sequence
nonsense mutation
change in nucleotide sequence results in a stop codon
RNA processing mutant
change in nucleotide sequence destroys RNA splicing site or creates a new splicing site
Small insertions and deletions are caused by
incorrect recombination (during meiosis - unequal crossover), strand slippage during replication, and intercalating agents
nondisjunction
incomplete separation of chromosomes in meiosis; changes number of chromosomes in cell - genome mutation
frequency of recombination between genes on same chromosomes is an
indicator of their proximity - shorter distance between genes = lower probability of crossover occurring
Trisomy
extra copy of a chromosome present - observed for chromosomes 13, 18, and 21 only
Monosomy
chromosome missing - if on an autosome it is lethal
Mosaicism
some of individual composed of normal cells, whereas other parts contain mutations - somatic mutations that occur during embryogenesis (earlier it happens = more mutant cells)
Strand-directed mismatch repair system
newly synthesized strand contains nicks that will be filled in later
Incorrectly paired bases cause distortion in DNA double helix - repair enzymes remove incorrect base pair and nucleotides to nearest nick - DNA polymerase fills in gap
Lynch syndrome (hereditary nonpolyposis colorectal carcinoma HNPCC)
Heritable cancer - high change of developing colorectal cancer
Caused by defects in mismatch repair system
DNA glycosylases
recognize specific types of altered base in DNA & catalyze their removal
AP endonuclease
recognizes that a base is missing and cuts sugar-phosphate backbone on side of missing base
DNA phosphodiesterase
removes deoxyribose phosphate group
Nucleotide excision repair
repairs damage caused by agents that result in large changes in the structure of DNA, i.e. pyrimidine dimers
Uses helicase/nucleases to separate and cut strand; polymerase and ligase fills in gap
xeroderma pigmentosum (XP)
Caused by mutations that abolish or impair function of proteins required for nucleotide excision repair
extreme sensitivity of skin to sunlight, pigmentation changes, and skin cancer
Nonhomologous end-joining
broken DNA ends (when both strands break) are brought together and ligated - causes loss of nucleotide at breakpoint
Homologous end-joining
recombination processes used to repair broken DNA without loss of information
Use other copy of chromosome to find sequence
Cyatarabine
Used to treat acute leukemias
converted to cytarabine triphosphate inside cells - competes with deoxyribonucleotides to bind to DNA polymerases
DNA replication and repair blocked
Cyclophosphamide
Used to treat Hodgkin’s lymphoma, lung, breast, and testicular cancers
Converted to phosphoramide mustard in liver - forms inter- and intra-strand DNA crosslinks, damage that blocks replication = cell death
Doxorubicin
Used against a variety of tumors
forms a tripartite complex with DNA and topoisomerase II - interfers with catalytic cycle and prevents re-ligation of double stranded breaks = cell death
