I think the rationale is that you have redundancy because normal cells have functional BRCA1/2 proteins and are thus able to compensate for the loss of PARP activity
this is late, but PARP inhibitors only affect BRCA1-/BRCA2- (BRCA deficient cells). BRCA deficient cells lack homologous recombination DNA repair mechanisms, so when we use PARP inhibitors, we prevent PARP from fixing nicks in single stranded DNA. Therefore, these BRCA- cells cannot fix the ssDNA break and these breaks become dsDNA breaks, and since the BRCA- cells also cannot use homologous recombination to fix those dsDNA breaks, the cells arrest in the cell cycle and apoptosis occurs.
PARP is a repair mechanism for single stranded breaks. BRCA is a repair mechanism for double stranded breaks. single stranded breaks become double stranded breaks. If you have one or the other, it gets fixed. Normal (noncancer) cells have working BRCA, so if you kill the PARP, they still work. Cancer cells don't have working BRCA, so if you kill the PARP, it dies.
@@ThatSecondDude im still a bit confused. correct me if i am wrong. BRCA MT causes failure to repair DSB and this leads to cell death. which Im assuming is great since cancerous cells are dying. why would we need parp-i when BRCA MT can already to that job ie causing cell death?
@@sreenbs from what i was taught, BRCA is almost like a backup for PARP; the way I see it is that PARP is a repair mechanism for smaller errors and therefore prevents it from becoming a bigger issue (like double stranded breaks, where BRCA is needed). also having 2 systems that are able to fix DNA is advantageous anyways as it would take so much more mutations to actually affect both systems. people who have brca1/2 mutations are already more susceptible to certain cancers because there is more chance for mutation due to there being one less system that fixes DNA damage, however treating cancer in these people also gives way to knocking out the main system that BRCA-deficient cells rely on for DNA repair - PARP. eliminating their main remaining way of repair would kinda finish them off. I guess the point is that lack of BRCA does not necessarily cause cell death as it still uses PARP for repair, therefore to finish the cell off, both mechanisms are ideally not active. hope this helps!
If we inhibit PARP don't we also inhibit the repair of healthy cells - which could lead to more cancer?
I think the rationale is that you have redundancy because normal cells have functional BRCA1/2 proteins and are thus able to compensate for the loss of PARP activity
this is late, but PARP inhibitors only affect BRCA1-/BRCA2- (BRCA deficient cells). BRCA deficient cells lack homologous recombination DNA repair mechanisms, so when we use PARP inhibitors, we prevent PARP from fixing nicks in single stranded DNA. Therefore, these BRCA- cells cannot fix the ssDNA break and these breaks become dsDNA breaks, and since the BRCA- cells also cannot use homologous recombination to fix those dsDNA breaks, the cells arrest in the cell cycle and apoptosis occurs.
So if we don’t use parp inhibitors, parp will continue to repair the cancerous cells?
So simple explanation to understand the concept. Thank you
I finally understand this concept, thank you so much!
Thank you! The animation is so cute and vivid~
love the animation, clears things up. Thank you!
good animation to teach easily👍🏻
A) excellent presentation of the mechanism; B) this lady needs to start an ASMR channel
Such a lovely video thank you very much! god bless you
An Amazing explanation
Great animation
the video image is too poor, you need to fix it more
Had an exam about this two weeks ago, wished I had stumbled upon this earlier
Thank you so much, made easy.
So easy to understand. Thanks
Easy to understand .
superrrrbbb ................easy to understand
It’s so nicely explained....
much thanks for the clear explanation..
Waaaaw i spend two days to know what PARP IS its beneficial for visual learners
Very well done!
Beautiful
Thank you
nice info
very well made!
Wow. Thank you
Cool, but what about non cancer, 99-95 percent of your body cels? they are gone too, arent they?
Thank you a lot!!!
simply perfect
Do PARP cells have any benefit to the DNA? If so what happens to the DNA needing to repair itself if the PARP all dies?
PARP is a repair mechanism for single stranded breaks. BRCA is a repair mechanism for double stranded breaks. single stranded breaks become double stranded breaks. If you have one or the other, it gets fixed. Normal (noncancer) cells have working BRCA, so if you kill the PARP, they still work. Cancer cells don't have working BRCA, so if you kill the PARP, it dies.
@@ThatSecondDude im still a bit confused. correct me if i am wrong. BRCA MT causes failure to repair DSB and this leads to cell death. which Im assuming is great since cancerous cells are dying. why would we need parp-i when BRCA MT can already to that job ie causing cell death?
@@sreenbs most likely some salvage pathway(s) to Brca1/2...
@@sreenbs from what i was taught, BRCA is almost like a backup for PARP; the way I see it is that PARP is a repair mechanism for smaller errors and therefore prevents it from becoming a bigger issue (like double stranded breaks, where BRCA is needed). also having 2 systems that are able to fix DNA is advantageous anyways as it would take so much more mutations to actually affect both systems. people who have brca1/2 mutations are already more susceptible to certain cancers because there is more chance for mutation due to there being one less system that fixes DNA damage, however treating cancer in these people also gives way to knocking out the main system that BRCA-deficient cells rely on for DNA repair - PARP. eliminating their main remaining way of repair would kinda finish them off.
I guess the point is that lack of BRCA does not necessarily cause cell death as it still uses PARP for repair, therefore to finish the cell off, both mechanisms are ideally not active. hope this helps!
THANK YOU
Just understand why its repair is not beneficial, Thanks a lot.
PAAAARRRRRP
It's a little scary to see a bunch of dead PARP dudes >_< wish they would have used something a little more scary to represent PARP.
cutee
Easy to understand.