4:Nucleic acids Flashcards
What are DNA and RNA nucleic acids?
DNA is deoxyribose nucleic acid - Nuclear/genomic DNA (Chromosomes); Used in the storage and transmission of genetic information.
RNA is ribonucleic acid; There are numerous types including mRNA (Messenger RNA code for proteins), rRNA(Ribosomal RNA form basic structure of the ribosome and catalyses protein synthesis), tRNA (transfer RNA central to protein synthesis as it acts as an adaptor between mRNA and amino acids) and snRNA (small nuclear RNA used in splicing and various other functions)
Both DNA and RNA are polynucleotides
What are the 3 major components of the central dogma?
DNA, RNA and proteins
Describe the composition of DNA and the polynucleotide chain that it forms
DNA is composed of nucleotides that contain 3 components;
5-carbon sugar (deoxyribose)
phosphate group
Nitrogenous bases - Purines (Double ring) = Adenine (A) and Guanine(G). Pyrimidines (Single ring) = Thymine (T) and Cytosine (C)
The polynucleotide chain formed has a 5’ to 3’ orientation. The 5’ end consists of a phosphate group and a hydroxyl group at the 3’ end of the chain. These groups allow for the formation of phosphodiester bonds to form between nucleotides, forming polynucleotides. 2 strands of polynucleotides form a twisted ladder known as the double helix structure. Along this structure, sugar and phosphate alternate along the sides of the ladder, linked via strong covalent bonds to form the ‘backbone’. Nitrogenous bases then attach to this backbone and form weak hydrogen bonds with their pair to form the ‘rungs’ of the ladder. A-T bond via 2 H-bonds and C-G bond via 3 H-bonds. Therefore, the abundance of pyridines and pyrimidines determine the ability of the bonds to separate. Therefore, the more pyrimidines present on the chain, the harder it is to separate the two strands and hence the more energy required to separate them.
Explain the RNA structure
The RNA nucleotide consists of a phosphate group, ribose sugar and four nitrogenous bases (A, G, C, U) - Uracil replaced thymine in RNA. Although the RNA is also a polynucleotide consisting of phosphodiester linkages; however it is only single stranded.
What are the 3 differences between DNA and RNA?
DNA vs RNA
Deoxyribose vs Ribose
Thymine vs Uracil
Double stranded vs Single stranded.
Describe the Watson and Crick Model of DNA replication.
DNA replication is a rapid process that yield is varied upon the species that it is occuring within.
The Watson and Crick Model is based on the Base-Pairing principle; Involving two new DNA strands copied from two old strands. (Semi-conservative model)
The general principle of DNA replication is that the two parental DNA strands are separated and serve as templates to generate new complementary DNA strands called daughter strands.
Describe the process of DNA replication
DNA replication starts at the origin (Initiation site) of replication; in Eukaryotes there are numerous origins, however in prokaryotes there is only one origin. The synthesis of the daughter strand occurs at the replication fork (site of unwinding and separation of the two strands. The leading strand is synthesis continuously in a 5’ to 3’ direction, while the lagging strand is synthesised dis-continuously by RNA primase synthases and an RNA primer to form small fragments known as ‘okazaki fragments’.
What are the 3 different methods anticancer drugs use to prevent DNA replication and cell division
1) Depleting the pool of nucleotides available. Eg; Methotrexate and Pentostatin
2) Inhibiting enzymes needed for the process Eg; Etopside (Stops DNA unwinding/separating)
3) Changing the structure of the DNA. Eg; Cisplatin (Stops DNA unwinding by crosslinking the two strands so they can’t be replicated) and Bleomycin (breaks DNA strands)
Even though cancer drugs are highly specific, they can act on the other cells within the body, hence resulting in the severe side effects that can be associated with chemotherapy drugs.
How do drugs that alter the DNA structure affect cancer cells?
Cross-linking agents prevent the separation of the two DNA strands, hence inhibiting the DNA replication process to continue. This stops the growth of the cancer. These agents can be alkylating (Eg cyclophosphamide) or platinum compounds (Eg cisplatin)
Describe the function of the antimetabolite anti-cancer drugs.
Antimetabolites deplete a pool of nucleotides available for the DNA synthesis and/or mi-incorporations.
This is done by purine antagonists (eg Mercaptopurine), pyrimidine antagonists (eg Fluorouracil) and Folic acid antagonists that block the formation of purines and hence stop growth (Eg methotrexate)
Describe the function of Topoisomerase inhibitors as anticancer drugs.
Topoisomerase inhibitors prevent the coiling and uncoiling of DNA by preventing the re-ligation of the DNA strand, so when the replication reaches this point the DNA breaks, hence stopping replication and DNA dissociates.
Eg. Irinotecan and topotecan
Describe the role of DNA helicase in eukaryotic DNA replication
The replication of DNA in eukaryotes require DNA helicase; It opens up the DNA double helix at the origin. However, this requires energy in the form of ATP (Adenosine triphosphate). This energy is produced by breaking the bond between the ribose and adenine base.
What is role of single-stranded binding proteins in the process of DNA replication?
They stabilise the DNA strands into a linear structure to avoid the formation of the tertiary DNA structures - The hairpin. Therefore, inhibiting the reformation of dsDNA. The bases are therefore exposed allowing DNA polymerase to efficiently copy the strand of DNA.
Explain DNA polymerases and explain the effect of the addition of the clamp to the complex.
There are 3 types of DNA polymerase (I,II,III).
They play a role in synthesising a new strand of DNA but can only work in the 5’ to 3’ direction.
By adding a sliding clamp to the complex, it helps DNA polymerase bind to the strand, hence improving it’s efficiency. I.e. with the presence of a clamp the polymerase can synthesise more residues before it dissociated (20 residues without the clamp but 500,000 with the clamp)
What are the 3 requirement of DNA polymerase II to synthesise a DNA strand?
- A DNA template strand
- A DNA/RNA primer to initiate the addition of the new bases (DNA polymerase is unable to initiate the process)
- A pool of nucleotides that can be added to the 3’ end of the synthesising DNA strand.
