L1: Genetic Principles of Medicine: Nucleic Acids, Genes, and Chromosomes Flashcards
genome
- the sum of genetic information for an organism
gene
- a specific sequence of DNA that encodes a specific protein
How much DNA in the human genome codes for proteins?
- low
- only around 1.2%
What is non-coding DNA used for
- needed to control expression of genes
Rank size of chromosome, gene, genome, and nucleotide
- nucleotide < gene < chromosome < genome
chromosome
- a single molecule of genomic DNA
genome of prokaryotes
- small, simple genomes
- circular or linear DNA molecules
genome of eukaryotes
- large genomes
- lots of extra DNA
- long, linear DNA molecules
origin of replication in prokaryotes
- single site of origin
origin of replication in eukaryotes
- large genome and multiple sites of origins of replication
What challenges do eukaryotes face due to their large genomes and linear chromosomes?
- because the genome is large, that makes it difficult to replicate
what happens as DNA strands are separated on one side of the fork?
- DNA on the other side becomes supercoiled
role of type I topoisomerase
- nicks one DNA strand to allow relaxation of supercoiling
- then seals the nick
role of type II topoisomerase
- makes double-stranded break in one duplex of DNA
- unbroken duplex is passed through ends of break
- break is sealed and enzyme releases DNA
template
- basis for instruction
origins of replication
- defined sites where replication begins
helicase
- unwinds DNA at fork
- present template for instruction
- breaks the Watson-Crick base pairs that form double helix
topoisomerases
- resolve knots and supercoils
- deals with increased helical tension in advance of the fork
SSB proteins
- stabilize unwound DNA that is now single-stranded
RNA primers
- initiate DNA synthesis
DNA polymerases
- make new DNA
ligase
- resolves Okazaki fragments
mismatch repair process
- certain DNA polymerases have exonuclease activity that can correct the mistakes
- cells are provided with the mismatch repair process when polymerase exonuclease activity fails
- mismatch repair process recognizes errors then correct those errors in the newly synthesized strand
- MSH2, MSH3, and MSH6 tasked with this
Lynch syndrome
- caused by mutations in the mismatch proteins
- limit the efficiency of the DNA repair process
- lead to inherited form of colorectal cancer (HNPCC)
role of centromeres
- guide accurate segregation during cell division
- spindle fibers attach and guide the chromosomes
role of telomeres
- protect ends of chromosome and guard against erosion from the ends
what is a telomere?
- short, repeated sequences found at the end of each chromosome
telomere as a buffer
- chromosomes have some sequence that acts as a buffer
- can be lost without losing any protein-coding genes
in which cells are the gene that encodes for telomerase present?
- all cells
when is the gene that encodes for telomerase expressed?
- in different cancers usually
- in stem cells
- NOT in neurons - those are post-differentiated
how does packaging of DNA work?
- DNA wrapped around histone octomer to form nucleosome
- further condensed until we get “beads on a string”
- packaged further
- regulated by post-translational modification of histones
what happens when DNA is highly condensed?
- it is not possible for transcriptional machinery to reach DNA
open DNA
- euchromatin
closed DNA
- heterochromatin
Eukaryotic nuclear DNA is organized into ________ chromosomes.
Linear
What ensures fast DNA replication in eukaryotic cells?
Multiple origins of replication.
Describe how DNA is replicated in Prokaryotes.
- Local opening of the double helix at a single origin of replication
- Formation of a replication bubble flanked by replication fork at each end.
- DNA replication occurs in a bidirectional manner
- 2 circular DNA molecules result, each containing one parental and one daughter strand.
During DNA replication, the _______ strand requires repetitive action of ligase to join DNA fragments.
Lagging
Caused by mutations in key DNA-repair factors and leads to a familial form of colorectal cancer.
Lynch syndrome.
Name 2 useful repetitive sequences in DNA.
Centromeres and Telomeres.
Function of telomerase.
Enzyme that adds repetitive sequences to the ends of chromosomes.
What is a nucleosome?
The basic unit of chromosome structure - contain DNA wrapped around a histone octamer.
How are nucleosomes packaged?
Nucleosomes are futher packaged on top of each other and folded into a series of loops, which are further condensed to produce the mitotic chromosome.
