Cell biology - theme 3 Flashcards
why might entry to interphase be delayed
delayed by entry into G₀ due to lack of mitogens to produce cyclin
what does cyclin do
activate cyclin dependent kinases (CDKs) to drive cell through cell cycle by phosphorylation
what do CDKs do
drive cell through cell cycle by phosphorylation
different CDKs for different phases of cell cycle
- S phase, increase S cyclin, increase CDKs for DNA replication
- M phase, increase M cyclin, increase mCDK activity
what can cause cancer
mutated p53 protein allows damaged DNA to be in daughter cells of mitosis so they are mutated
what does p53 protein do
DNA damage activates p53 to inhibit CDKs to block cell cycle at G1 to allow DNA repair
excessive DNA damage activates p53 to stimulate Bax to trigger apoptosis
apoptosis
programmed cell death caused by cascade of intracellular caspases
how is apoptosis suppressed
suppressed by mitogens and growth factors
general steps for apoptosis
Fas ligand binds to cell with Fas receptor
cascade of intracellular caspases
cleaves cytoskeleton so detaches from adjacent cell
cell shrinks
DNAses fragment DNA
membrane changes to trigger phagocytosis
cell engulfed and digested by macrophages
how does mitochondrial injury lead to apoptosis
damaged mitochondria leak cytochrome-c
cytochrome-c activates caspases
necrosis
accidental cell death caused by acute physical and chemical injury
steps of necrosis
cell swells and bursts (lysis)
releases contents
triggers inflammatory response
damage
non-disjunction
what does it cause
homologous chromosomes do not separate so one cell has none and other has two
aneuploidy and polyploidy
aneuploidy
loss or gain of one or more chromosomes
trisomy
e.g. Down’s, Edward’s
type of aneuploidy where 1 chromosome is gained
Down’s 21
Edward’s 18
monosomy
e.g. Turner’s
type of aneuploidy where 1 chromosome is lost
Turner’s lack of X or Y
polyploidy
addition of one or more complete haploid chromosomes
triploidy
type of polyploidy where 3 of each chromsome so 69 chromosomes
translocation
a piece of chromosome form one homologous part breaks off and join chromosome from a different pair
what prevents G1 -> S phase
p27 protein inhibits CDKs
germline mutations
occur in germ cells/ gametes
inherited disease
somatic mutations
occur in somatic/ adult cells during development or adult life
not inherited
dominant-negative mutation
loss of function due to interference of mutant gene product with normal gene product of corresponding allele
types of nucleotide deletion mutations (3)
multiple of 3 (codon) - in frame deletion removes one amino acid
not multiple of 3 - frameshift loses protein expression and function
larger deletions - partial/ whole gene deletion, complete loss of protein expression and function
types of nucleotide substitution mutations
by replacement of nucleotide (2)
transition - substitution of same base type e.g. purine for purine
transversion - substitution of different base type e.g. purine for pyrimidine
types of nucleotide substitution mutations
effect of gene/ protein expression/ function (5)
silent - codes for same amino acid, no effect
missense - encodes different amino acid
nonsense - introduces stop codon
splice site - aberrant splicing results in exon skipping or intron retention
promoter or regulatory element - altered expression levels
errors in DNA repair (4)
mismatch repair - corrects mismatched bases in DNA replication
nucleotide excision repair - removes thymine dimers and DNA adducts
base excision repair - removes abnormal bases
post replication repair - removal of double stranded breaks by homologous recombination
chemical damage to DNA e.g.
alcohol, toobacco form DNA adducts cause depurination (deletion) or deamination (substitution)
physical damage to DNA e.g.
ionising radiation e.g. X rays causes double strand breaks
UV light form thymine dimers
causes of DNA mutation
DNA replication errors by proofreading mistakes of DNA polymerase
chemical damage
physical damage
errors in DNA repair
mutation of sickle cell anaemia
beta globin mutation A-T transversion
GAG -> GTG so Glu to Val
mutation
DNA variant with frequency <1% population
polymorphism
DNA variant with frequency >1% population and must have two alleles
e.g. single nucleotide polymorphism (SNP)
polygenic traits
influenced by other genes
multifactorial traits
influenced by interaction of genetic and environmental factors
