Genetic errors due to DNA polymerase

Amelia Molina MorenoMedicine Student 3rd semester

DNA CONTAINS ALL OF OUR GENETIC

INFORMATION

• IN ORDER FOR IT TO HAVE IT COMPLETE IT

MUST SUFFER A REPLICATION

SEMICONCERVATIVE

The REPLICATION is the process of the DNA were he copies in order to be transmited, in this proces it obtaines two molecules of daughter DNA formed by a original fork and a new

fork.    . .

The diference that researcher has found with other cancers is that children with this syndrome develop more mutations than any human cancers by far (20,000 mutations in six months) .

'biallelic mismatch repair deficiency' (bMMRD)

But this little step is the responsible

of several syndromes

WHICH CAUSES:1. multiple brain tumors2. Lymphomas3. gastrointestinal cancers by the age of 10

“Ultimately, we hope this leads to treatments to avoid the presently inevitable consequences of this predisposition syndrome”

• One of the biggest problems this kids have is that they dont count with an specific treatment, becouse scientist create treatments for more common cancers.

This study will help the scientist so they could do more targeted treatments and will be a huge advanzed for prevention of cancer

• This study identifies a secondary mutation which occurs only in tumor cells in an enzyme called polymerase, which is a second safeguard that helps to effectively repair mutations while the DNA replicates.

• The combination of these two mutations leaves patients with no ability to repair mistakes that may occur while DNA is replicating, and causes a rapid wave of cancer that the investigators have dubbed the "great flood."

• This has important implications for both diagnosis and targeted treatment of this devastating disease

• This study provides a major step forwards in understanding why certain children are more susceptible to developing multiple cancers.

• Allows us to understand the steps that lead to cancer developing

• Our findings indicate the genetic driver that causes this 'great flood' of cancer mutations in patients with bMMRD. The secondary mutation in the enzyme polymerase causes a unique signature of mutations that is present in 100 per cent of the cases.

“We were able to describe how many mutations develop, how fast they occur, how many mutations the tumor can sustain, and the type of mutation that occurs, which we found is unique to bMMRD cancers"

• The biggest goal achieve during this study was to take a deeper look at this cancer predisposition syndrome and for the first time they are able to tell the story of how this cancer develops.

HOW?

The Children's Brain Tumour Research, Using genetic and clinical information and tumour samples gathered from each patient.

THIS NOT ONLY MEANS AN ADVANZED ON DIAGNOSIS AND TREATMENT IT ALSO HELPS SCIENTIS TO UNDERTAND THE STEPS IT TAKES TO DEVELOPE CANCER IN GENERAL.

• Because the high number of mutations is so specific to bMMRD syndrome, researchers are able to detect children who are carriers just by sequencing the tumor.

• "If the child has a very high number of mutations then we know immediately that they have this cancer predisposition syndrome,"

NEW LIGHT

HOW NATURALLY OCCUR MUTATIONS IN OUR DNA?

University of Edinburgh researchers developed a method to label -- and track -- pieces of new DNA as they are made and to identify which copying enzyme is responsible.

The study of how DNA replicates has shown how it change over time and how our genome has been shaped over evolution and has revealed that some of the genetic switches that control when genes are activated are likely to be hotspots for DNA flaws, or mutations, to develop.

One of the multiple causes are

Copying enzimes

One of the most important is the Polymerase

• One polymerase first makes short stretches of DNA that act as a scaffold so that the other copying enzymes can then replicate the remaining DNA.

• As this scaffold DNA contains errors, the standard model assumed all of it was removed during the process

• These scaffold sections, and the mistakes they contain, become trapped in the DNA.

WHY?

• This often ocurrs at points in the important regulatory switches. These sites are therefore more likely than other regions to have trapped scaffold DNA and its associated errors.

• Mistakes in these crucial step of genetic sequences can change or destroy the regulatory switch, which can lead

1. To genetic disease2. Alter susceptibility to common diseases 3. Contribute to the development of cancer.

The new goal of researchers?

• That this new achieve helps understanding why mutations happen and more complete to see these in regions were it doesnt codify for proteins.

• If the scientists could find the cause of why the DNA is unable to identify the error and repare it, we could be talking about a new light of treatments using as a target the DNA Polymerase

“We have been aware of striking patterns in how DNA changes for several years but couldn't explain why the patterns were there”

This study gives:

1. mechanism and revealed previously unseen patterns

2. Point to sites in our DNA that are likely to have a high rate of damaging mutations.

If scientist focus in those points were damaging mutations are most likely to occur they they can create treatments more specific and not so common for al cancers o genetic diseases.

WHATS NEW?

• Groups of scientist have created a new method to track polymerase enzymes that copy our genome.

• This shows us that despite DNA replication is an amazingly accurate process, errors do occur and most of all in very important parts of our genome

Our genome has also been part of evolution, during it

our genome has been shaped into our needs but also giving space to new

mutations never seen before.

• But the questions will be

1. Why the process that is in charge of controling flaws in the DNA replication is unable to recognize all of them ?

2. Why some people are more suceptible for mutations?

Those are answers that our advanced medicine and technology are searching for

In conclusion…

Error DNA

Regulation point

doesnt detect the

error

Polymerase replicates

A MUTATION IS NOW IN THE DAUGHTER DNA

Observations 1. When we know and understand how our DNA replicates it help us to

understand how our genome has been change over the evolution even more it help us to see were the most common errors occur and to see specifically which enzyme is the responsible for the mutation

2. Medicine is getting to see which are the steps that’s the cancer does to develop also they could diagnosis before we are born and create treatments more specific for those kids who are more susceptible to multiple cancers