Theme 3 - DNA and chromosomes Flashcards
What phase of the cell cycle do cells spend most of their time?
interphase
What three things happen in the gap phases?
growth, get ready for replication and accumulate ATP
how big are interphase chromosomes?
30nm (no unwound but not mitotic)
what is the purpose of 30nm fibre structure in interphase?
allows DNA to be replicated/transcribed
what phase does one a single chromatid become two sister chromatids?
S phase - DNA replication
what forms at the centromere and what is the function of this?
kinetochore - Attaches to spindle microtubules when chromosomes get pulled apart
what is the state of the nuclear membrane in prophase
the nuclear membrane is still in tact
what happens to chromosomes in prophase
they condense from the 30nm fibre into mitotic chromosomes
in what phase do mitotic spindles starts to form?
prophase
at what stage does the nuclear membrane disintegrate and spindle microtubules attach to kinetochores
prometaphase
what causes chromosomes to line up on the equator?
tension of the pull of the kinetochores by microtubules
what binds sister chromatids together?
cohesins
at what stage do cohesins that bind the sister chromatids together disintegrate?
anaphase
give another type of microtubule apart from kinetochore microtubules
astral microtubules
give two key events of telephone
chromosomes have arrived at the poles and the nuclear envelope reforms
how are organelles assigned o each daughter cell in cytokinesis?
randomly
what two molecules control the cell cycle
cyclins and cyclin dependent kinases
in what phase does p53 check for DNA damage?
G1
what phase do most chemotherapy drugs target?
S phase
how many base pairs need to be replicated for a cell to divide?
6 billion
how many nucleotides are replicated per second?
100/s
why does DNA replication run from 5’ to 3’
because the strands are polar
why does the semi conservative nature of DNA replication mean that mutations will be passed on?
DNA unzips, hydrogen bonds are broken then each strand acts as a template
what end are nucleotides added on to in DNA replication?
3’
what bond forms between new nucleotides as they are added to the growing DNA strand in replication?
a strong covalent phosphodiester bond
how many origins of replication are there on one DNA strand at any given time?
10,000
why is there discontinuous synthesis on the lagging strand in DNA replication?
the 3’ end is moving away from the replication fork - creation of Okazaki fragments that are all joined together
what is the action of DNA polymerase in DNA replication?
adds nucleotides to the growing strand
what is the action of DNA helicase in DNA replication?
unwinds the DNA
what is the action of DNA primase in DNA replication?
adds an RNA primer which allows polymerase to bind and move from 5 to 3
what is the action of nucleases in DNA replication?
remove the RNA primer
what is the action of DNA ligase in DNA replication?
joins small gaps together
what mutation causes Werner syndrome?
mutation in a minor DNA helicase (WRN)
what is the usual effect of mutations in mitosis or DNA replication genes?
lethality
what is the incidence of Werner syndrome?
1 in 200,000
what are the symptoms of Werner syndrome?
premature ageing - accumulation of diseases of old age in 40s/50s eg cataracts, atherosclerosis, cancer
what underpins the mechanism of Werner syndrome?
mutation in DNA helices causes errors in DNA replication and repair - slower replication and more damage is introduced
what two mechanisms prevent accumulation of mutations in DNA replication
proof reading and excision repair systems
how many mistakes per DNA multiplication probably occur?
6
what is an internal cause of DNA damage?
products of normal cell function eg oxygen free radicals
what are three external causes of DNA damage?
benzene, cigarette smoke and UV/ionising radiation
what does DNA nuclease do in excision repair?
come in and cuts out the bad base pair region
what does DNA polymerase do in excision repair?
adds in the correct base once the incorrect one has been removed
what does DNA ligase do in excision repair?
bandages all the gaps once the correct base has been inserted
what enzyme proof reads DNA?
DNA polymerase
what group does the DNA polymerase detect when nucleotides are in the wrong place?
3’ hydroxyl group - if its not where its supposed to be the base is removed by a nuclease
Xeroderma pigmentosa is due to a mutation in what?
UV repair system
what bases are implicated are Xeroderma pigmentosa?
two adjacent thymines
what is the problem in XP?
UV light causes a covalent bond between them to create a dimer which is usually repaired by mechanisms that remove the dimers - XP dont have a UV repair system so this can’t happen
what is the implication of XP?
children are acutely sensitive to sunlight, hypo/hyper pigmentation and multiple cancers at a young age
how frequent are mutations in the population
occur <1% of the Time
what is a synonymous SNP?
causes no change in the amino acid sequence therefore no bearing on the disease state
what is a non synonymous SNP?
changes the amino acid sequence
give three example of monogenic diseases and the type of mutation that causes them
sickle cell (substitution), CF (deletion) and Huntingtons (insertion)
what type mutation characterises SCA and where is it found?
single nucleotide substitution in the beta globin HBB gene (A to T on chromosome 11)
what is the incidence of SCA in the UK?
12,500
what type mutation characterises CF and where is it found?
3 base pair deletion (70% patients) on chromosome 7
how many cases of CF are there in the UK?
9000
what is the implication of deletion mutation in the CFTR gene?
CFTR channel is not transported correctly or expressed in the right place therefore there is impaired chloride transport
what type mutation characterises Huntington’s and where is it found?
insertion mutation on the Huntingtin gene on chromosome 4
what are the symptoms of huntingtons?
uncontrolled muscle movement, loss of memory, depression, difficulty swallowing and speaking
what does a mutation in Huntingtin cause?
increased numbers of CAG repeats which stick together and is toxic to nerve cells
what number of CAG repeats is normal?
6 to 35
what number of CAG repeats would a carrier of Ht have?
36-39
what number of CAG repeats would a Ht sufferer have?
> 40
what essential process becomes a problem when there are more than 36 CAG repeats in Ht?
DNA replication
what is the incidence of Huntington’s in the uk?
7000
