DNA replication and Inheritance of genes Flashcards
What main enzyme carries out DNA replication?
-DNA polymerase
Why does DNA need to be replicated?
-In order to produce an identical daughter cells
What does helicase do?
-Unwinds the DNA molecule for replication
What is the substrate of DNA replication?
-dNTPs
In which direction does chain elongation occur?
-Growth is in 5’->3’ direction
At what stage of the cell cycle does DNA replication occur?
-S phase
Why is DNA replication described as semi-conservative?
-One parent strand in each daughter cell
How is initiation of DNA replication defined?
-By origins of replication
What is the end product of DNA replication?
-Two DNA molecules
What are the two strands named during DNA replication?
- Leading strand
- Lagging strand
How are the two strands synthesised (in what manner?)
- Leading strand is synthesised continually
- lagging strand is synthesised discontinually
Why is the lagging strand synthesised discontinuously?
-The lagging strand is synthesised discontinually because elongation occurs in a 5’->3’ drection. As helicase unwinds, DNA pol binds nearest the site where DNA is still wound and works backwards on itself as this is the 5’-3’ direction of the new strand. As helicase unwinds some more and DNApol has finished that segment, it unbinds and rebinds further down the strand
What does the lagging stand produce and what enzyme is needed?
- Okazaki fragments
- Ligase to join the fragments together
What two bonds are involved in the addition of a dNTP and where?
- Phosphodiester bond between a phosphate of one dNTP and the -OH at C3
- Hydrogen bonds between the complementary nitrogen bases
Describe cell cycle
- G0= resting phase (non-dividing cells; some cells can pass to G1)
- G1= cell content replication
- S= DNA replication
- G2= double check and repair
- 0=interphase
- M= cell division
Where are the two cell cycle checkpoints in cell cycle?
-Between G1:S and G2:M
Describe initiation of DNA replication
- Helicase unwinds DNA creating replication fork
- Primase binds to the strand to be replicated, adding a primer to the strand and recruits DNA pol
- Simultaneous recruitment of specific proteins
- DNA pol replication begins
Describe the process of elongation during DNA replication
- Helicase unwinds DNA
- Primer and DNApol bind and move towards the 5’ ends of the strands, adding complementary dNTPs
Where will the primer be located in the new strands of DNA?
-At the start at the 5’ end
Describe termination of DNA replication
- There are several DNApol on one DNA molecule due to there being multiple origins of replication, and thus multiple replication forks
- When replication forks meet, DNApol unbinds and elongation stops
- The separate stand segments produced by the various replication forks are fused together by DNA ligase to produce one continuous molecule of DNA
What is the end result of DNA replication
-Pair of sister chromatids connected by a centromere -> still called a chromosome
What determines the position of the centromere?
-It is sequence dependant
In what cells is mitosis used and what is its purpose?
- In somatic cell lines
- To produce 2 identical daughter cells
At what stage of the cell cycle does mitosis occur and which processes have already happened?
- Happens in M
- G1, S and G2 already occured
Name locations where mitosis is necessary?
- Epidermis
- Mucosae
- Bone marrow
Describe prophase of mitosis?
- Breakdown of nuclear membrane
- Spindle fibres and centrioles appear
- Chromosomes condense
- C46, SC92
Describe prometaphase
- Spindle fibres attach to chromosomes
- Chromosomes condense
Describe metaphase in mitosis
-Chromosomes align by random assortment (In any order) at the metaphase plate
Describe anaphase in mitosis
- Centromeres divide
- Sister chromatids move to opposite poles (Each cell receives a mC1 and a pC1; they are identical)
Describe telophase in mitosis
- Nuclear membrane reforms
- Chromosomes decondense (euchromatin)
- Spindle fibres disappear
- Cleavage furrow appears
Describe cytokinesis
- Cytoplasm divides
- Parent cell becomes two daughter cells
- C46, SC46
What is a kinetochore?
-Protein complex structure which binds the centromere to the spindle fibres
What is the purpose of meiosis?
-To produce 4 non-identical gametes, i.e sperm and egg
What are the two main differences between mitosis and meiosis?
- Meiosis has one round of replication but then two rounds of division
- Meiosis produces cells with haploid chromosome number
Describe prophase I of meiosis
- Disintegration of nuclear membrane
- Spindle fibres appear
- Chromosomes condense
- C46, SC92
What is crossing over?
-The exchange of maternal chromosome material with paternal chromosome material between non-sister chromatids
What are non-sister chromatids?
-Chromatids of non-homologous pairs within the same tetrad, eg mC1 and pC1
What is the result of crossing over?
-Results in chromosomes with mixed genetic material
Describe metaphase I of meiosis
-Independant assortment of chromosomes at the metaphase plate
ie
-Sister chromatids find there homologous pair and form a tetrad at the metaphase plate
-Crossing over occurs
Describe independent assortment in metaphase I of meiosis
-Homologous pairs of chromosomes find each other and line up to form a tetrad, i.e. mC1 finds pC1 and line up
Describe anaphase I of meiosis
- Tetrad divides as spindle fibres retract (no splitting of centromeres)
- One daughter cell gets mC1 and other gets pC1 and so on
Describe telophase I
- Nuclear membrane reforms
- Spindle fibres disappear
- Cleavage furrow
- 2 non-identical daughter cells produced
- C23, SC46
Describe prophase II of meiosis
- Nuclear membrane disintegrates
- Spindle fibres appear
- C23, SC46
Describe metaphase II of meiosis
-Chromosomes with sister chromatids randomly assort on the metaphase plate
Describe anaphase II of meiosis
- Spindle fibres contract
- Sister chromatids separate
- Each cell will only be haploid
- They will be non-identical due to crossing over of tetrads
Describe telophase II of meiosis
- Nuclear membrane reforms
- Chromosomes decondense to exhibit euchromatin
- Spibdle fibres disappear
- Cell Division
- C23 SC23
What are the consequences of meiosis?
- Generates genetic diversity through independent assortment and crossing over
- Maintains the chromosome number as two haploid cells fuse during fertilisation
How long does spermatogenesis take?
-approx. 48 days from spermatid to mature sperm
What is different about oogenesis?
-Only one gamete becomes a mature ovum, the rest become polar bodies
What happens if crossing over does not occur?
- Crossing over is essential
- Without crossing over sister chromatids will not separate
- Produces empty gametes and some with double genetic info
Faulty meiosis is the leading cause of…
…mental retardation
Define genotype?
-Genetic make up of an individual as either a whole, or for one specific gene locus
Define phenotype
-All the observable characteristics of an individual or the observable trait as a result of the genotype at one (or more) specific loci
How can environmental factors affect the phenotype?
-Environmental factors can influence and overcome the genotype and therefore alter the natural phenotype
Define gene
-A unit of hereditary; a length of DNA on a chromosome which codes for a protein
Define allele
-An alternate form/copy of a gene
List some environmental factors which can effect genotype/phenotype
- Radiation
- Mutagens
- Chemicals which effect growth
- Diet
- Lifestyle
- Infection
What are the 5 different patterns of inheritance?
- Autosomal recessive
- Autosomal dominant
- X-linked recessive
- X-linked dominant
- Y-linked
Define homozygous
-Two alleles of the gene are the same (homozygote)
Define heterozygous
-Two different alleles of the same gene (heterozygote)
Define hemizygous
-Only one allele of the gene on the X chromosome (males only)
Define dominant allele
-The allele which determines the phenotype
Define recessive
-Th non-dominant allele
Describe autosomal recessive inheritance, give an example
- Heterozygotes are not effected but are said to be carriers
- males/females affected equally
- Disease can appear to skip generations
- Two homozygotes will have an affected offspring
- Cystic Fibrosis
What is the chance of two heterozygotes for an autosomal recessive trait having an affected offspring?
-25%
Describe autosomal dominant inheritance, and give an example
- Heterozygotes will be affect
- Males/females affected equally
- Rarely found in homozygous state -> disease usually too severe to take to term
- Every affected individual will have at least 1 affected parent
- Disease can not skip a generation
- Huntingtons disease
What are the chances of two heterozygotes for a autosomal dominant trait having an affected offspring?
75%
Describe X-linked recessive inheritance, and provide an example
- Homozygous females affected
- All males affected
- Males affected more than females
- Every affected female will have an affected father and at least a carrier mother
- Affected males can not give trait to sons
- Unaffected daughters of affected males will be carriers
- Haemophilia A
What is the chance of a heterozygous female for an X-linked recessive trait producing an affected son?
-50%
Describe X-Linked dominant inheritance
- All heterozygotes affected
- Males/females affected equally
- Affected males have an affected mother
- affected daughter has at least one affected parent
Describe co-dominance inheritance using an example
- Alleles work together to produce phenotype
- ABO blood typing (Isoglutamine genes code for glycoproteins on RBC surface)
- I has three alleles (A, B and O)
- IA dominant over O
- IB dominant over O
- Neither IA or IB are dominant over each other; they are codominant
What is complementation, provide an example
- When two different genes complement each other to produce the final phenotype
- Albinism
- Recessive inheritance
- The two genes both have two alleles
- Complement offspring will be heterozygous for both alleles
- One genotype complements for faulty genotype of the other
When are genes said to be linked?
When they are on the same chromosome
Why do linked genes not show independent assortment?
-genes can not go into different gametes as they are on the same chromosome, especially if they are close together as this reduced the chance of crossing over
What is recombination?
-The process by which two genes exchange information resulting in the production of a new combination of alleles
What is recombination frequency and how is it calculated?
- The frequency with which a single chromosome cross over will take place between 2 genes, dependant on the distance between those genes
- X-linked only use males because you can be 100% sure that their phenotype is correct
- Look at the first recombinant generation and count the males affected in that generation and every affected generation after
- Count the number of recombination events in the first recombinant generation
- That is the frequency
- Hint: Recombination is usually identified in X-linked when a male has both disease traits but the father is normal
