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Stephen P. Bell (MIT / HHMI) 1a: Chromosomal DNA Replication: The DNA Replication Fork
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- เผยแพร่เมื่อ 18 ส.ค. 2024
- www.ibiology.o...
Part 1a: Mechanisms of Chromosomal DNA Replication: The Replication Fork: For an organism to survive, its DNA must be accurately and completely copied during each cell division. Bell explains how replication begins at the DNA replication fork.
Part 1b: Mechanisms of Chromosomal DNA Replication: Initiation of Replication: Bell describes how the multi-enzyme replisome identifies the correct site for the initiation of DNA replication and begins to copy the chromosomal DNA.
Part 2: Single-Molecule Studies of Eukaryotic DNA Replication: Stephen Bell’s lab determined, at the level of single molecules, the sequence of events which initiate eukaryotic DNA replication.
Talk Overview:
Every time a cell divides, its genomic DNA must be completely, accurately and rapidly duplicated. This feat is completed by an amazing, multi-enzyme nanomachine, called the replisome. The replisome includes one DNA helicase, one RNA polymerase and three DNA polymerases, as well as numerous non-enzymatic proteins, all of which work together at the DNA replication fork. In Part 1a, Dr. Bell gives an excellent, step-by-step description of the function of each replisome protein at the bacterial replication fork.
In Part 1b, Bell focuses on the initiation of DNA replication. At the site where replication begins, chromosomal DNA is separated into two single strands. Two replisomes are then assembled on the DNA and they move away from each other in opposite directions. Bell describes how the sites for the initiation of replication are identified, how the helicase is loaded and activated, and how the replisome is assembled. As he explains, these events are significantly more complicated in eukaryotes than bacteria.
In his last talk, Dr. Bell describes an assay developed in his lab to study eukaryotic DNA replication at the single molecule level. Using this assay, Bell’s lab has determined the detailed process by which eukaryotic DNA helicase loads on DNA and begins the replication process.
Speaker Biography:
Dr. Bell is Professor of Biology at the Massachusetts Institute of Technology and an Investigator of the Howard Hughes Medical Institute. His lab studies the assembly of multi-protein complexes called replisomes that are responsible for replicating eukaryotic chromosomal DNA, and the regulation of this process to ensure that each chromosome is accurately and completely replicated just once per cell cycle.
In recognition of his contributions to the field, Bell was awarded the National Academy of Sciences Award in Molecular Biology and the ASBMB/Schering-Plough Scientific Achievement Award. Bell has also received the MIT Everett Moore Baker Memorial Teaching Award and the School of Science Teaching Prize for Excellence in Undergraduate Education. Bell is co-author of the popular Molecular Biology of the Gene textbook.
Bell received his BA in biochemistry from Northwestern University and his PhD in biochemistry from the University of California, Berkeley where he worked with Robert Tjian. He was a post-doctoral fellow with Bruce Stillman at Cold Spring Harbor Laboratory before moving to MIT.
Learn more about Dr. Bell’s research at his MIT and HHMI sites:
web.mit.edu/bel...
www.hhmi.org/sc...
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Finally something more than BASIC !! thank you!
That was really great! Now I know DNA from the very beginning DNA strand, DNA polymerase, Primase, DNA holoenzyme Pol III, DNA Holder, DNA Sliding Clamp, T, synthesize DNA, base pairs, template (toppled into a Primer-Template Junction) (PTJ), helicase, ATP hydrolyzed and the release of junction and clamp occurs.
Its so annoying that people get to think they know dna from very beginning by watching a single video on TH-cam...
Order of reaction and thermodynamic parameters?... ∆G and binding energy?...
Enzyme kinetics?... Nothing is explained in all aspects.. So when you say you know the dna from the start you're wrong...
@@jackyjack9660 You just gave me douche chills. Why not give her some encouragement for being curious and excited about the topic and tell her there's a lot more interesting tstuff to learn about rather than stifling her enthusiasm?
@@patldennis preach
This is absolutely brilliant, thank you so much! I was completely overwhelmed when I first saw the DNALC video elsewhere, and although it was amazing to watch, I wasn't sure how I was going to learn how any of it worked. Watching it again at the end of the video, I could immediately recognise and name the units :)
Sorry my stupid question below, I see if eg ATP transport fails, then no attachment of the sliding clamp, via the loaders , yes?
Thanks for such a clear talk
So the sliding base clamp here is paramount. Under what natural conditions (if any) does this fail or are we only talking experimental conditions, in order to elucidate the mechansim(s) here?
Simply epic, imma show it to everyone at my molecular biology class
Po
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Thanks for explaining the various types of dna. Great lesson will rewatch!
Awesome presentation I really enjoyed watching it as an update on replication and please know I’m a trombone player
I understand that the DNA clamps speed up polymerase activity, is it really necessary for the lagging strang to have a DNA clamp? Okazaki fragments are short and shouldnt really require many bases be added. The way it looks in the presentation is that there is a DNA clamp for each Okazaki fragment, how are they all removed?
this until in the loop when the direction is from 5`-3` the polymerase must synthesis the dna strand thats why we need clamp there too and when the pol reaches to the other primer it falls off
So how did this evolve? I mean how did the DNA evolve machines that read and replicate it? How is it possible for mutations to come up with such a complicated Intelligent process? Blows my mind.
It couldn't evolve. But you are not allowed to say that :-)
Over time traits that increase replication should become more common. Seems like probabilities to me.
Heard initially organisms used RNA for genetic info and enzymes, but then it specialized into DNA (more stable than RNA) for genetic information, and amino chains for enzymes (it is unclear to me why aminoacids became enzymes, but I imagine the choice of 20 bases as opposed to 4 made for more differentiation).
Think I need some remedial DNA training. Got my Okazaki fragments confused with my polymerases : (
Is there a video explaining about DnaA , DnaC and helicase?
One error per 10^10 replicated base pairs is absolutely ASTOUNDING! The whole design is astounding.
Yet if there were no errors we'd all be genetic clones. Sharing that status with you gives me cold chills. Perfect polymerases obviously are selected against since none are. and wouldn't a supernatural polymerase have 0 errors?
Thank you for reviving my old comment,
@@patldennis. It's fun to see that six people agreed with me, probably shortly after I posted it four years ago.
It's not clear what point you're trying to make. From prior comments, I assume you're trying to squirm out of the reality of a supernatural creator, regardless of the overwhelming evidence. If that's your aim, you're doing a poor job.
We don't know what would have happened had the first couple, in their perfect state, had not sinned. Some theorize that polymerase only became erroneous after that. It seems logical, but there's no data and no way of analyzing it. No experiment is possible, so science must remain mute on that topic.
@@KenJackson_US 6 people agreed with you but look at all the similiar comments that got more likes. Too bad you didn't have the balls to be more explicit in terms of supernatural jibber jabber.
@@KenJackson_US How does sin affect the function of polymerase?
You missed the key points, @@patldennis. I said, _"We don't know ..."_ And also, _"... , but there's no data and no way of analyzing it. ..., so science must remain mute on that topic."_
its my second favorite professor from MIT! (the first is Erik lander)
Wild! Great effing lecture, my man.
Sure sounds a lot like a technical lecture involving complex engineering. Imagine trying to design such a complex system then building the various components using bio or synthetic chemistry.
A very nice talk.
But is this in eukariot?
Thanks Sara Thornton
2:40 "Bumbling mass of mutagenised cells" is a great insult!
We need another series of Blackadder.
Or maybe say cancer lol
Great video! Thanks!
Thank you !🙏
How does the Topoisomerase evolve? If it requires ATP to operate how does it do so during this evolutionary process?
Well in light of the fact that there are multiple topoisomerase in any cell; species or taxon it's pretty obvious they evolved based on their sequence relationships- individual topoisomerase types take on more specific functions in derived taxa. If it uses ATP it is probably a member of the ATPase superfamily of proteins which do lots of different things but have an ATP hydrolyzing domain in common with additional domains tacked on over time.
ok, that one error bugs me.
Poor guy when reading the script lol! The course is amazingly helpful tho. thanks
What happens with 5' primer ?
Ribonuclease H recognizes the specific topology and cuts it out. Short length repair polymerases can then fill that in with DNA.
How the ter tus complex replicate DNA ?
it does not replicate DNA, it stops the replisome in procaryotes from replicating more than half (or a little more) of the cccDNA
Do you have notes for this
سبحان الخالق العظيم!
Individuals that don’t believe there is a God I hope this kind of knowledge that is passed on to you will change your mind.
Please contact me want to
Have more information as assembly , vaccines as much DNA replication as possible thankyou thus far
Helicase runs on leading strand
That is what I was taught as well, maybe this is a newer understanding?...
Out of curiosity what level of education is the demographic watching videos like these?
1 year of technical college general cell biology class
He's wrong. There's much more DNA in the human body.
You could go back and forth to the sun 500 times instead of just once.