L6 Cell Biology
🧠 Concepts Introduced
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Learning Objectives • Describe the basic unit and structure of DNA and chromosome • Explain the details of DNA replication process • Explain how cells maintain DNA fidelity in replication
DNA as a unit of inheritance
nucleoside contains only sugar and a base nucleotide contains sugar, base and a phosphate group nucleic acid long molecule made up of smaller molecules called nucleotides
A T C G
RNA also differs from DNA in that it bears a hydroxy group in the 2ʹ position
DNA structure
phosphodiester bond between sugar and phosphate group
protein bind on DNA on major groove cuz the space is big major and minor groove
DNA & Chromosomes
How can the human genome, which is about 30× larger than the C. elegans genome, have roughly the same number of genes?
evolution has 2 round of genome duplicaton (entire genome is duplicated) thats why it increases in size. but why gene in small number - a lot of repetative sequence
in human, one gene can code for hundreds of protein (alternative splicing) thats why protein pool expands in human compared to other species
DNA condensation
Nucleosome
positive histone and negative DNA is electrostatic
Chromatin
two form of chromatin solenoid or zigzag structure (observed in vivo- outside of the cells, cant view it in the cells so it looks different)
H1 histone make contact with DNA that just about to wrap the histone when DNA coming out from the wrapping (acts like a lock)
Chromosome scaffold
fold chromatin into a loop to save space
have different names such as SAR and MAR but they mean the same
chromatin attach to the scaffold
only gene exposed outside of the loop is active (can be binded for transcriptions)
Condensin in scaffold
introduce the supercoil
locks the loop (condensation)
condensin II come first which is already present in nucleus condensin I is made in cytoplasmic they work with condensin II they dissociate when they come back with G1
Cohesin
cohesin locks two sister chromatids together
DNA replication
during DNA replication it makes mistakes all the time which can lead to permanent mutation (wrong base, miss a base)
2 ways to fix this: DNA repair OR DNA polymerase in eucaryotic cells can repair the mistakes
Initiation
separate double strand to single strand single strand can be used as template (template is the assisting DNA strand to copy new DNA strand)
DNA replication start in bubble. the bubble will become bigger and bigger
replication go in two directions simultaneously
proteins needed: DNA helicase - to unwind the DNA. it sits in the replicaton fork
single straded DNA-binding proteins - to make sure the DNA do not anneal back
DNA primase - synthesize RNA primers (first protein that starts synthesized)
Topoisomerase - regulate the overwinding or underwinding of DNA by cutting and rejoining the sugar-phosphate backbone
replication origin has a very specific sequence to initiate the replication there are many replication origin to replicate much faster
Why is a primase (making RNA instead of DNA), rather than a DNA polymerase used to initiate DNA replication? to form primer-DNA primate
Why is a primase, rather than a DNA polymerase used to initiate DNA replication?
- Primase can start synthesizing RNA primers without needing a pre-existing 3' OH group, unlike DNA polymerase, which requires an existing primer to extend.
- Primase synthesizes RNA primers, which are distinct from DNA and can be easily recognized and later removed by cellular machinery, preventing permanent incorporation into the genome.
Elongation
DNA polymerase from 5' to 3'
leading strand is the existing strand (template) eg. 3' to 5' then synthesize new strand 5' to 3'
lagging strand (discontinuous) with a lot of short fragments
PCNA act as a clamp holding on to DNA and DNA polymerase tgt to not let go
DNA polemerase alpha cannot to DNA repair
last DNA ligase join the ogazaki fragments
Okazaki maturation
Termination & Telomere Replication
after so many cell division then get shorter and shorter that reaches genes that code for proteins which leads to problems
RNA primer with DNA polymerase
apurinic side is with backbone , gives signals to chop off backbone
