https://youtu.be/ohm-avnDYcM
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https://youtu.be/h_1QLdtF8d0
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https://youtu.be/O4SdDuBnoW4
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https://youtu.be/UXI3_tbsi0E
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https://youtu.be/O7TQm67yqIk
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https://youtu.be/oefAI2x2CQM

شوية ملخصات 😁

* chromatin =Total number of chromosomes
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* DNA is a polymer of deoxyribonucleoside monophosphates
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* The nucleotides in same strand are linked by 3__5 phosphodiester bond
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* 5 end (the end with free phosphate)
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* 3 end (the end with free hydroxyl)
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* 3 end & 5 end are not attached to other nucleotides
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* hydrophilic deoxyribose-phosphate is on outside
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* hydrophobic bases are stacked inside
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* always written in sequence from 5 to 3
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* The major & minor grooves of strands
( for the binding of regulatory proteins )
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* Actinomycine D (Anticancer drug)
(intercalating into the minor groove of DNA and block at path of helicase)
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* The base pairs are perpendicular to the axis of helix
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* chargaff Rule 👌
(adenine=thymine) & ( guanine=cytosine)
&(total amount of purines = total amount of pyrimidines )
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* The base pairs are held together by hydrogen bonds
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* Two hydrogen bonds between A&T
* three hydrogen bonds between G&C
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* The loss of helical structure in DNA called denaturation
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* DNA can reform the double helix by the process called renaturation or reannealing
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* B form is a right handed helix with 10 nucleotides base pairs per turn
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* A form a right handed helix with 11 nucleotides base pairs per turn
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* Z form (zigzags) ( rich C&G)
a left handed helix with 12 nucleotides base pairs per turn
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* chromatin in prokaryotes is (single circular supercoiled double stranded)
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* chromatin in eukaryotes (46 chromosome linear double stranded)
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* Eukaryotes heve closed circular DNA in mitochondria
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* genome in prokaryotes are ~(4 million)
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* genome in eukaryotes are ~(3 billion)
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* plasmid (present in prokaryote)
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* plasmid is (nonchromosomal DNA)
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* plasmid (carries genetic information & antibiotic resestant gene )
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DNA Replication in prokaryotic?

⃣مصطلح (Replication)
* Transfere of genetic informations from parental cells to doughter
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⃣* replication occur at S-phase of cell cycle
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⃣مصطلح (semiconservative replication )
* two strands of DNA double helix are separated and each can replication and
produces two daughter molecules

ملاحظة: كل dughter DNA عندها خيط جديد(complementary) وخيط قديم (Template)
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⃣*اهم حاجات تبيهم عملية ال Replication
- Single strand (old strand)
- primer (RNA piece)
- ATP , GTP , CTP , TTP
- Enzymes (polymerase , helicase ,ligase, topoisomerase )

ملاحظة : بالنسبة ل mitochondrial DNA ماتبيش primer
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⃣اهم مثال على prokaryotic replication هي E.coli
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⃣origin of replication (ori C)
* site includes a short sequence
* Exclusively of AT base pairs
* contain 13 base pairs
* start by (GATC)

وفي نقطة البداية هذي حيجيها بروتين اسمه
(dna A protein)
هو اللي بيبدأ في فصل الخيطين ويبي ATP
باش يكون حاجة اسمها replication bubble


ملاحظة : بالنسبة لل eukaryotes عنده أكثر من مكان يبدأ بيه ال replication مش مكان واحد
مهمة هلباااااااااااااااااااااااااااااااااااااااااااا
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⃣مصطلح Replication fork
* When two strands unwind and separate they form V shaped
واللي بدير اللقطة هذي انزيم اسمه helicase
وحيستهلك 2ATP في كل H-bond يكسرها

لكن لما الانزيم هذا بيفتح الخيطين حيسبب مشكلة
واللي هي positive supercoil حيجي بطل انزيم حينقذ الموقف ويفك العقدة اللي تكونت واللي هو انزيم اسمه Topoisomerase
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عندنا نوعين من Topoisomerase
⃣Topoisomerase type I
* cut 1 strand of DNA
* do not use ATP
* inhibited by antitumours drug
* relax negative supercoil

ملاحظة: اللي عند الeukaryotes يخدم على الزوز
positive & negative supercoil
______________________________________
⃣Topoisomerase type II (gyrase)
* cut 2 strands of DNA
* use ATP
* inhibited by Antibiotics drug
واهم مثال Ciprofloxacin
* relax positive supercoil
ملاحظة: غير موجود في ال human
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⃣both Topoisomerase
* used replication &transcription & recombination
* has endonuclease & ligase
* used tyrosine
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⃣single-stranded -binding proteins
* keep the two strands of DNA seperate
* protect DNA from nucleases enzyme
______________________________________

⃣* Replication of double strand DNA is bidirectional
يعني حيكون عندنا 2replication fork & 2helicase
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⃣DNA polymerase
* copying the DNA template (parental)
* elongate a new DNA strand
* read from 3 to 5
* synthesis from 5 to 3
* cannot initiate synthesis without prime
______________________________________
⃣DNA polymerase type III
* هو اللي بيبدأ في تصنيع الخيط الجديد ويركب الnucleotides
* Highly processive enzyme
* has beta subunit
* في كل قاعدة يركبها يحتاج ل 2ATP
* hydrolysis of pp to 2p
* irreversible
______________________________________
⃣* DNA synthesis stops when that nucleotide is depleted
______________________________________
⃣primer RNA
* 10 nucleotides long
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⃣primase enzyme
* specific RNA polymerase
* synthesized primer
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⃣Leading strand
* start copied advancing replication fork
* synthesized continuos
* used one primer

⃣Lagging strand
* start copied away replication fork
* synthesized discontinuos
* with small fragments of DNA (okazaki)
* used multi of primer
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⃣proofreading of DNA (misreading)
* يعني لو صار خطأ في تصنيع DNA مثلا ركبنا قاعدة غلط يجي انزيم ينحيها اسمه exonuclease
هذا يخدم من 3 الي 5 ...بعد ماينحيها يجي من جديد DNA polymerase type III ويصنع في مكانها وطبعا نعرفوه يخدم من 5 الي 3 فقط
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Excision of RNA Primers and replacement by DNA
عندنا انزيم ثاني اسمه Exonuclease لكن هذا يخدم من 5الي3 شن بدير !!!
حينحي ال primer RNA كيف بالزبط !!
حيكسر nucleotide of RNA اللي في الحاشية
وبعدين يكمل ال endonuclease ويفترش من داخل واخيرا يجينا المنقذ البرنس الفالح اللي اسمه
DNA polymerase type I يعبي القواعد ويصنع DNA في مكان RNA واللقطة هذي اسمها
Gap filling

ملاحظة : حتي هني حنديرو proofreading ونستخدمو exonuclease متع من 3الي5
______________________________________
⃣DNA ligase(used 2high energy )
* requires energy from NAD (prokaryotic)
* requires energy from ATP (eukaryotic)

______________________________________

🌟🌟🌟🌟🌟🌟تحت السطر 🌟🌟🌟🌟🌟🌟
⃣Retroviruses
* used Reverse transcriptase (RNA-dependant DNA polymerase)
* used tRNA as a primer

______________________________________
⃣Actinomycin-D (anticancer drug)
* physical block
* inhibition replication &transcription

______________________________________
⃣DNA polymerase type III
* major replication enzyme

______________________________________
⃣DNA polymerase type I
* major repair enzyme

______________________________________
⃣positive supercoiling
* left handed coil
* clock wise

______________________________________
⃣negative supercoiling
* right handed coil
* anti clock wise
__________________________________

DNA repair:

-if there's mispair (one or more than one nucleotide(either base ,or the whole nucleotide), and this happened each day in one cell about a million mismatch escape the proofreading property of DNA polymerase.
_agents which cause mutations or alteration could be
endogenous(mainly by replication system mispair)
exogenous(by radiation,chemicals,UV light,free radicals....etc)
_ newly synthesized strands aren't methylated,so this is use to identify ,and diffrentiate b\w them and parental strand(v.imp).
-excinuclease v.imp identify and excise the dimers by UV specific endonuclease.
-xeroderma pigmentosum v.imp
_correction of base alteration :
cytosine is deaminated to uracil by nitrous oxide,there will removal of base(uracil)by uracil N glycosylase(can recognize ) and Apyrimidinic site is formed,then apyrimidinic endonuclease will cut the strand ,so the lyase will cut in order for DNA poly can work and ligase will seal both parts of the strand.
_repair of ds. breaks :
those breaks caused by radiation and free radicals or gene rearragements.
-house keeping genes breaks is lethal
-high eupkaryotes(plants and animals)
-lower euokaryotes(monocellualar ,fungi ,viruces,algae)
-there's no repair in transcription
RNA is single strand of ribonucleac acid
functions of different RNA are imp
DNA mutation is replicated b\c genetic material of DNA is preserved as it is.
and,this will result may may be in producing supraactive enzyme or non functioning one.
in 5 prime of mRNA there's a cap(protect from exonucleases)and it's consists of methyl guanosine triposhpate,and recognition
in 3 prime ther's poly A tail also protect from exonuclease actitvity.
rRNA is part of ribosomes(rRNA+proteins)
tRNA transfer of A.As and contain anticodon that recognize the seqense of nucleotide in order to put the right A.As on

mRNA production occur in nucleus,but it's function in ribosomes and it's giuded by special eupkaryotic str. that exist in the 5 prime end a chemical str. called cap and it exist for two purposes:
(protection\recognetion).
Genome : all DNA that is present in organism
the number of nucleotides(bp): it's not proportional to number of genes ,it doesn't mean that the more chr. the more the number of genes .
there's no different in gens b\w human (healthy individuals)
-gene expression=transcription+translation(in case of protein only)
because for example tRNA ,rRNA,and snRNA are only transcribed.
-RNA polymerase synthesize the RNA strand in direction of 5prime to 3 prime
-promotor is never transcribed(receive receptor hormone complex ,and regulate the process)
-the genes and promoters are the same in each cell for the same gene ,but what make the promoter start a transcription of same genes differntly is the transcription factors and acticvators
-holoenzyme:is very imp. recognize promoter region.
-difference b\w replication &transcription is very imp.

ملاحظات الدكتور أحمد زايد :
1- The step with the highest rate of errors during protein synthesis is: the elongation step.

2- Peptidyltransferase is a ribozyme (part of the 23s/28s rRNA) NOT A PROTEIN

3- During Translation the a.a. are added from the COOH end
(The end that is attached to the 3' end of tRNA)

4- Chaperones are important for the folding of large** proteins not small ones.

5- Some genetic diseases are due to incorrect signal*** peptides (The a.a. seq that are responsible for protein targeting)

6- ما قالهاش الدكتور لكن هكي حسيتها مهمة+ نبي نتفكرها 🐣
Translation can be inhibited by the phosphorylation of eIF-2 which inactivates the factor.

7- eIF-2-GTP Factor & others in eukaryotes (IF-2-GTP in prokaryotes) is responsible for the recognition of the initial*** aminoacyl tRNA
*Which will be placed directly in the P site*

8- tRNA attaches to the a.a. by its 3' end

و توه نبدو في التجميعات 😎

heme abd albari .pdf

تفريغ أول ثلاث محاضرات د.أحمد زايد Gene Expression.

المحاضرة الرابعة من الجين

lecture4
DNA repair:

-if there's mispair (one or more than one nucleotide(either base ,or the whole nucleotide), and this happened each day in one cell about a million mismatch escape the proofreading property of DNA polymerase.
_agents which cause mutations or alteration could be
endogenous(mainly by replication system mispair)
exogenous(by radiation,chemicals,UV light,free radicals....etc)
_ newly synthesized strands aren't methylated,so this is use to identify ,and diffrentiate b\w them and parental strand(v.imp).
-excinuclease v.imp identify and excise the dimers by UV specific endonuclease.
-xeroderma pigmentosum v.imp
_correction of base alteration :
cytosine is deaminated to uracil by nitrous oxide,there will removal of base(uracil)by uracil N glycosylase(can recognize ) and Apyrimidinic site is formed,then apyrimidinic endonuclease will cut the strand ,so the lyase will cut in order for DNA poly can work and ligase will seal both parts of the strand.
_repair of ds. breaks :
those breaks caused by radiation and free radicals or gene rearragements.
-house keeping genes breaks is lethal
-high eupkaryotes(plants and animals)
-lower euokaryotes(monocellualar ,fungi ,viruces,algae)
-there's no repair in transcription
RNA is single strand of ribonucleac acid
functions of different RNA are imp
DNA mutation is replicated b\c genetic material of DNA is preserved as it is.
and,this will result may may be in producing supraactive enzyme or non functioning one.
in 5 prime of mRNA there's a cap(protect from exonucleases)and it's consists of methyl guanosine triposhpate,and recognition
in 3 prime ther's poly A tail also protect from exonuclease actitvity.
rRNA is part of ribosomes(rRNA+proteins)
tRNA transfer of A.As and contain anticodon that recognize the seqense of nucleotide in order to put the right A.As on