What happens to a cell if a chromosome gets damaged

[icakeov]

Hi, I was wondering what would happen to a cell if one of the chromosomes gets destroyed or damaged in a section?

I am guessing that, if the "housekeeping genes" and expressed genes are intact, the cell, would be ok or somewhat ok?

If it can survive, would it affect its ability to do mitosis, or does a cell divide regardless of what "state" the chromosomes are, as long as the cell is alive?

Thanks!

 

[jim mcnamara]

Some points:
Depending on the tissue and stage of development of plants or animals, cells may:
never divide,
sometimes divide,
divide as a part of everyday function.
Damaged DNA generally means the death of a cell. The survival rate is low, usually.
Chemicals that damage DNA are often categorized as teratogens when the targeted organism is an embryonic human.

https://en.wikipedia.org/wiki/Teratology

 

[icakeov]

Great, thanks Jim!

 

[BillTre]

There are many ways a chromosome could get damaged. Some are:

1. Sequence information is lost because of a bunch of changes in the base pair sequence (point mutants or small deletions). This would destroy its ability to code for it normal functions. Cell function would then be impaired or it might die. Depends on the nature of the genes involved (housekeeping or not).
   
2. The chromosome structure is messed up (such as broken into pieces) but the sequence and functions encoded by it are still present in the cell. This could remain alive and function. The small parts could act like small pieces of chromosomes or plasmids, but would not behave well during cell division because not all the pieces would be linked to the centromere which directs the chromsome's movements during mitosis or meiosis. However, if the cell were to divide the daughter cells would most likely lose some pieces of the chromosome or perhaps gain some extras pieces. This could lead to cell death or loss of cellular functions. Treating cancer with radiation breaks up chromosomes. Because cancer cells divide quickly they preferentially die. Any imbalance in the ratios of the numbers of particular genes can cause problems (especially in higher organisms requiring the use of encoded more complex developmental processes).
   
3. Chromosomes may also have more complex disruptions due to breaks forming but being repaired (due to cellular DNA repair mechanisms) but not quite being repaired properly. Here is a list of some possible weird chromosome structures that might result. If this results in inversions or other weird situations, the cells may have problems similar to #2 due to crossing over. This could result in having zero or one centromere connected to a piece of chromosome. The results in these cases could be immediate in the next division or might cause accumulating problems over several divisions. This is information I think is best conveyed through pictures, like this one. Additional pictures can be found by googling "inversions and cell division" or other related terms. Genetics texts should also have explanations of these situations.
   
4. Lacking teleomeres could lead to the chromosome getting a bit shorter with each division it undergoes. This could also lead to the gradual development of problems accumulating over time.
   
5. There are probably other ways problems could occur.

 

[icakeov]

Incredible! Totally answered it! Thank you Bill!

 

[Ygggdrasil]

Cells have the ability to sense DNA damage and arrest the cell cycle until the damage is repaired. This helps prevent damaged nucleotides from being incorrectly copied during DNA replication and helps prevent chromosome from being improperly sorted during mitosis. If the cells prove unable to repair the damage, the cell will activate apoptosis—programmed cell death—in order to remove the damaged cell from the body. Problems correctly identifying DNA damage can lead to the accumulation of many damaging mutations and lead to cancer. In fact, many of the genes that are frequently mutated in cancer (e.g. p53, BRCA, DNA polymerase E) are involved in DNA repair.

Here's a chapter on DNA repair from a cell biology textbook: https://www.ncbi.nlm.nih.gov/books/NBK26879/

 

[icakeov]

Hi a have a bit of a follow up question, it is in regards to the "DNA repair" mechanisms mentioned above.

I was wondering if there are any "protein repair" mechanisms after translation and transcription are fully completed. I know that they still have to go through some "final" processes in the cytoplasm but, once they are "fully completed", are there any cellular "protein repair" (not destruction) mechanisms that would "repair" the proteins?

And if there were, which I am guessing likely aren't, how would they know what state to bring the protein into? I would ask this same question about "DNA repair" mechanisms, how do they "know" what to "fix" damaged DNA "into"? Do they just patch it up with whatever they have and then that will determine if the DNA will continue to function or not?

Many thanks for feedback!

 

[jim mcnamara]

Transcription and translation - steps to making a protein from DNA - is not goof-proof. It has an error rate:
http://book.bionumbers.org/what-is-the-error-rate-in-transcription-and-translation/

The cell has a clean up mechanism - what happens to the junk protein? @Ygggdrasil may have a good link for this. I'm not in a place to do much looking now.

Here is a not-simple answer to what happens when proteins fail to fold correctly:
http://swift.cmbi.ru.nl/teach/folding/index.html

 

[Ygggdrasil]

Hi a have a bit of a follow up question, it is in regards to the "DNA repair" mechanisms mentioned above.

I was wondering if there are any "protein repair" mechanisms after translation and transcription are fully completed. I know that they still have to go through some "final" processes in the cytoplasm but, once they are "fully completed", are there any cellular "protein repair" (not destruction) mechanisms that would "repair" the proteins?

And if there were, which I am guessing likely aren't, how would they know what state to bring the protein into? I would ask this same question about "DNA repair" mechanisms, how do they "know" what to "fix" damaged DNA "into"? Do they just patch it up with whatever they have and then that will determine if the DNA will continue to function or not?

Many thanks for feedback!

There are not protein repair mechanisms inside of the cell but there are protein quality control mechanisms. Proteins with errors or damage are problematic when they become misfolded, and the cell can recognize these misfolded proteins and destroy them.

DNA repair mechanisms are able to know how to fix damaged DNA because DNA has two strands, which enables errors to be recognized as a mis-paired base pair. Damaged nucleotides can be recognized, removed, and the other DNA strand encodes the information to enable the cell to fill in the correct sequence at the site of damage. During DNA replication, the cell has mechanisms to know which strand is the original strand and which strand is the copy to know which strand to repair if an error is made during DNA replication.

In the case that damage alters the sequence on both strands of the DNA (for example, in the case of radiation-induced double-stranded break in the DNA), the cell makes use of the fact that we carry two copies of each chromosome. The information from the second chromosome can be used to repair the damaged chromosome.

 

[jim mcnamara]

@Ygggdrasil okay.
Consider:

In the case that damage alters the sequence on both strands of the DNA (for example, in the case of radiation-induced double-stranded break in the DNA), the cell makes use of the fact that we carry two copies of each chromosome. The information from the second chromosome can be used to repair the damaged chromosome.

What happens in alternation of generations when the "dominant" phase of the organism is not diploid, but haploid instead? Apoptosis?

What I'm really asking - is this the driving force behind polyploidy? Improved DNA repair?

 

[Ygggdrasil]

@Ygggdrasil okay.
Consider:

What happens in alternation of generations when the "dominant" phase of the organism is not diploid, but haploid instead? Apoptosis?

What I'm really asking - is this the driving force behind polyploidy? Improved DNA repair?

There are two main pathways for double stranded break repair: non-homologous end joining and homologous recombination (see the diagram from my https://www.physicsforums.com/insights/dont-fear-https://www.physicsforums.com/insights/dont-fear-crispr-new-gene-editing-technologies-wont-lead-designer-babies/-new-gene-editing-technologies-wont-lead-designer-babies/). Homologous recombination copies the information from the extra copy of the chromosome onto the damaged chromosome. This can even work in haploid organisms provided that the organism is in the G2 phase of the cell cycle and has copied its DNA in preparation for cell division.

In the case where a homologous copy of the chromosome is not available, the cell can perform non-homologous end joining where the two ends are simply stitched together. Often, DNA sequence is lost and mutations can be introduced. However, as only about 1% of the human genome codes for protein and only about 10% is evolutionarily conserved, these mutations may not have any major effects on the cell.

The cell also has methods to sense DNA damage and know whether or not it has been repaired. The cell will arrest the cell cycle to prevent DNA replication and cell division until the damage has been repaired and if the damage cannot be repaired, the cell will undergo apoptosis.

 

[icakeov]

Super helpful! Thank you!

 

[BillTre]

@Ygggdrasil okay.
Consider:

What happens in alternation of generations when the "dominant" phase of the organism is not diploid, but haploid instead? Apoptosis?

What I'm really asking - is this the driving force behind polyploidy? Improved DNA repair?

When there is a haploid generation, there will be stronger selection against any recessives or haploid insufficient loci. The recessives would be "revealed (normally they are hidden as recessives behind the other alleles and are therefore cryptic)". Any haploid insufficient (often deletions of part of one of the chromosome (could be small), leaving only one gene to do all the work in a diploid organism, which sometimes works OK), would similarly be exposed to stronger selection. These cases of stronger selection could be severe enough to cause death (a lethal) or reduce or eliminate reproductive ability (a sterile). This should result to some extent in the reduction of these mutations of the population's genetic background.
These mutations should only affect their organism, if they are expressed or have some function during the time when they are haploid. The same thing would apply to our haploid sperm and egg cells, however, these cells could be loaded up with gene products from neighboring cells or from their lineal precursors (the cells they came from).

For many cases, it is probably not the driving force behind polyploidy.
One case, in Drosophila salivary glands (a specific tissue) there is extreme polyploidy (maybe 2,000 x). My understanding is that this tissue specific polyploidy is to support the larger metabolic activity of those cells, but not sure).

Several organisms (like sunflowers) are polyploid as a result of hybridizing. In cases like these, I would guess that the immediate driving has to do with the mechanics of cell division and chromosome segregation.

Polyploid producing events can produce a lot of extra gene copies.
The lineage leading to us humans has undergone two rounds of whole genome duplications, However, we are not octiploid (8x) because most of the duplicate genes are either modified to new and different functional products or are not maintained by selection a(to maintain the older function(s) of the gene), while the second copy can then be modified (either in the encoded gene product or in the non-transcript-encoding control sequences) to assume evolutionary new functions through a minimal amount of sequence changes.
Because fewer changes are required to generate a meaningful (meaning adaptive) new gene, this speeds up evolution.