Faithful cell division requires tightly controlled protein placement

S A R A A R A N G O V A L E N C I A

M E D I C I N E S T U D E N T

Faithful cell division requires tightly

controlled protein placement at the centromeres and

Diagnostic criteria for Christianson Syndrome.

1. Whitehead Institute forBiomedical Research. "Faithfulcell division requires tightlycontrolled protein placement atthe centromeres." ScienceDaily.Science Daily, 17 July 2014<www.sciencedaily.com/releases/ 0107/140717124517.htm>.

2. Brown University. "Diagnosticcriteria for ChristiansonSyndrome." ScienceDaily.ScienceDaily, 21 July 2014.<www.sciencedaily.com/releases/2014/07/140721100416.htm>.

Faithful cell division requires tightly controlled protein placement at the centromeres and Diagnostic criteria for Christianson Syndrome.

Molecular biology

Teacher:Lina Maria MartinezSanches

Sara Arango ValenciaMedicine student3rd semester

July28, 2014

CENP-A is an important centromeric protein that ensures a normal mitotic division. Ranks Histone H3 in the nucleosome chromatin at kinetochore level, so it’s implicated in the correct chromosomal segregation and distribution during the

phases of mitosis.

Medical Utility

Bibliography

The CS, even though it ‘s a little known disease, can

provide important information about autism

because it’s highly related to this pathology

A new study provides the most definitive characterization of the autism-like intellectual disability disorder Christianson Syndrome and provides the first diagnostic criteria to help doctors and families identify and understand the condition. Initial evidence suggests CS could affect tens of thousands of boys worldwide

Faithful cell division requires tightly

controlled protein placement at the

centromeres

There are about 30 billion, and in every mitosis, the initial DNA should be divided precisely between two resulting cells. Many copies of the CNP-A protein protects the centromere .The cell's DNA is copied and condensed into chromosomes paired, and need to secure a copy of this protein for each. Although this rehearing of CNP-A occurs in the G1 phase, and remains a mystery. Kara McKinley,'ve identified the molecular controls that ensure that CENP-A deposition at centromeres occurs in the right place and the right time. Microtubules extending from opposite sides of the cell and attached to the kinetochore, which is anchored by molecules CENP-A at the centromere. This allows the printing of the centromeres during mitosis phases. If many or few chromosomes have centromeres, or they are in the wrong place, chromosome segregation fails, and the cell dies or becomes ill. McKinley found that two kinases - Plk1 and CDK –are in charge of the correct rehearing of CENP-A, so, the protein fills every empty space in the centromere. Through these kinases, McKinley was able to disrupt the replenishment of CENP-A and cause severe problems for the segregation. "Kara's work defined the basic control replenishing of CENP-A" says Cheeseman, professor at Massachusetts Institute of Technology. "Since this step is a vital part of a centromere, his work is a major advance in the way we think about it as a process."

The CENP-A integrated into human DNA at the centromeres on each chromosome, has a vital role in cell division. New work describes how the tightly controlled replenishment of CENP-A progresses. "The assumption was that the timing of CENP-A replenishment had to be important for centromeres function because it was so tightly controlled.

INTRODUCTIONChristianson Syndrome was only first

reported in 1999 and some symptoms take

more than a decade to appear, families

and doctors urgently need fundamental

information about it. A new study that

doubles the number of cases now

documented in the scientific literature

provides the most definitive

characterization of CS to date. The authors

therefore propose the first diagnostic

criteria for the condition.

In conducting their study, which includes

detailed behavioral, medical and genetic

observations of 14 boys with CS from 12

families, the team of scientists and physicians

worked with families of the small but fast-

growing Christianson Syndrome Association.

In their study, Morrow's team was able to

quantify the most frequent symptoms specific

to CS. These include intellectual disability,

epilepsy, difficulty or inability walking and

talking, attenuated head and brain growth, and

hyperactivity. Boys sometimes exhibit other

symptoms -including autism-like behaviors-

that the researchers include as secondary

proposed diagnostic criteria.

Morrow said there’s evidence that SLC9A6

mutations - and therefore CS - may be a

relatively common source of X-linked

intellectual disability.

Diagnostic criteria for

Christianson Syndrome

My opinion: This protein is not only important toprotect the centromere, it provides a succesfullmitosis; wich is primordial for evade some patologies

My opinion: I think that is still much to discover about the disease and its treatment. And medicine need to improve the way of life of this people.

A new study provides the most definitive characterization of the autism-like intellectual disability disorder Christianson Syndrome and provides the first diagnostic criteria to help doctors and families identify and understand the condition. Initial evidence suggests CS could affect tens of thousands of boys worldwide

The CENP-A integrated into human DNA at the centromeres on each chromosome, has a vital role in cell division. New work describes how the tightly controlled replenishment of CENP-A progresses. "The assumption was that the timing of CENP-A replenishment had to be important for centromeres function because it was so tightly controlled.

INTRODUCTION

En la mitosis se requiere la proteína CENP-A que se depositará en el lugar correcto. Cuando las dos

quinasas responsables de la regulación de este proceso - CDK y Plk1 - están bloqueados, las células

en división tienen defectos mitoticosgraves, incluyendo mal alineamiento cromosomico y husos multipolares,

en comparación con las células normales.

A new study of 14 boys with CS of 12 families of the Christianson

Syndrome Association, the team of scientists. In their study, Morrow's team was able to quantify the most frequent symptoms specific to CS.

Faithful cell division requires tightly controlled

protein placement at the centromeres

There are about 30 billion, and in every mitosis, the initial DNA should be divided precisely between two resulting cells. Many copies of the CNP-A protein protects the centromere .The cell's DNA is copied and condensed into chromosomes paired, and need to secure a copy of this protein for each. Although this rehearing of CNP-A occurs in the G1 phase, and remains a mystery. Kara McKinley,'ve identified the molecular controls that ensure that CENP-A deposition at centromeres occurs in the right place and the right time. Microtubules extending from opposite sides of the cell and attached to the kinetochore, which is anchored by molecules CENP-A at the centromere. This allows the printing of the centromeres during mitosis phases. If many or few chromosomes have centromeres, or they are in the wrong place, chromosome segregation fails, and the cell dies or becomes ill. McKinley found that two kinases - Plk1 and CDK – are in charge of the correct rehearing of CENP-A, so, the protein fills every empty space in the centromere. Through these kinases, McKinley was able to disrupt the replenishment of CENP-A and cause severe problems for the segregation. "Kara's work defined the basic control replenishing of CENP-A" says Cheeseman, professor at Massachusetts Institute of Technology. "Since this step is a vital part of a centromere, his work is a major advance in the way we think about it as a process."

My opinion: This protein is not only important to protectthe centromere, it provides a succesfull mitosis; wich isprimordial for evade some patologies

Faithful cell division requires tightly controlled protein placement at the centromeres

Whitehead Institute for Biomedical ResearchJuly 17, 2014



Images of cells with normal and abnormal CENP-A deposition. Centromere (red) location and proper division of chromosomes (blue) by microtubules (green) in mitosis require the protein CENP-A to be deposited in the correct place. When the the two kinases responsible for regulating this process--CDK and Plk1--are blocked, dividing cells have severe mitotic defects, including dramatically misaligned chromosomes and multipolar spindles (right), compared to normal cells (left).

During division of any of the body's roughly 30 trillion cells, DNA from the initial cell must be split precisely between the two resulting cells. Critical to successful cell division is the integrity of the centromere



For the segregation machinery to recognize this region, it must contain many copies of a pivotal protein known as CENP-A.

Each time the cell makes a copy of its DNA in preparation for cell division, it needs to ensure that the centromeres of the new and old DNA strand get re-filled with CENP-A.

Cheeseman's lab has identified the molecular controls that ensure that CENP-A deposition at centromeres occurs in the right place at precisely the right time.

The fate of the cell depends on this process going smoothly. If the chromosomes have too many or too few centromeres, or the centromeres are located in the wrong place, proper chromosome segregation fails



My opinion: This protein isnot only important to protectthe centromere, it provides a

succesfull mitosis; wich isprimordial for evade some

patologies



Diagnostic criteria for Christianson SyndromeBrown University

July 21, 2014

Christianson Syndrome was only first reported in 1999 and some

symptoms take more than a decade to appear, families and doctors

urgently need fundamental information about it. A new study that

doubles the number of cases now documented in the scientific

literature provides the most definitive characterization of CS to date.

The authors therefore propose the first diagnostic criteria for the

condition.

In conducting their study, which includes detailed behavioral, medical

and genetic observations of 14 boys with CS from 12 families, the team

of scientists and physicians worked with families of the small but fast-

growing Christianson Syndrome Association.

In their study, Morrow's team was able to quantify the most frequent

symptoms specific to CS. These include intellectual disability, epilepsy,

difficulty or inability walking and talking, attenuated head and brain

growth, and hyperactivity. Boys sometimes exhibit other symptoms -

including autism-like behaviors- that the researchers include as

secondary proposed diagnostic criteria.

Morrow said there’s evidence that SLC9A6 mutations - and therefore CS

- may be a relatively common source of X-linked intellectual disability.

Diagnostic criteria for Christianson Syndrome

My opinion: I think that is still much to discover about the disease and its treatment. And medicine need to improve the

way of life of this people.

These scans show atrophy of the cerebellum in a boy with

Christianson Syndrome. This symptom was observed in some, but not

all boys, with the condition.


July 21, 2014

Morrow's team was able to quantify the most frequent symptoms specific to CS. These include moderate to severe intellectual disability, epilepsy, difficulty or inability walking and talking, attenuated head and brain growth, and hyperactivity.

Many CS traits, including a very happy disposition, appear similar to those of another autism-like condition, Angelman Syndrome, but the study defines important differences.

Tagged Christianson syndrome. The image shows the neural growth.

Boys have a mutation on the SLC9A6 gene on the X chromosome that disables production of a protein called NHE6 that is important for neurological development.

Girls, who have two X chromosomes, can also be carriers of CS mutations, but they appear to be affected differently and less severely or not at all, the study reports.


July 21, 2014

"If we assume that between 1-3 percent of the world's population is diagnosed with an intellectual disability and approximately 10-20 percent of the causes are due to X-linked genes, then we can estimate that CS may affect between 1 in 16,000 to 100,000 people"

The connection to the SLC9A6 gene was first discovered in 2008. In analyzing the genomes of each patient and their parents in the new study, they found that each boy had only one mutation, but there were many different ones across the entire group.


July 21, 2014

Diagnostic criteria for Christianson Syndrome

Brown UniversityJuly 21, 2014

In a paper published last year, Morrow's research group found that NHE6 is underexpressed in the brains of many children with more general forms of autism. This potential connection suggests that learning about CS can help doctors and scientists learn about autism.


July 21, 2014

My opinion: I think that is still much to discover about the disease and its treatment. And medicine need to improve the way of life of this people.

CENP-A is an important centromeric protein that ensures a normal mitotic division. Ranks Histone H3 in the nucleosome chromatin at kinetochore level, so it’s implicated in the correct chromosomal segregation and distribution during the

phases of mitosis.

Medical Utility

The CS, even though it ‘s a little known disease, can

provide important information about autism

because it’s highly related to this pathology

CENP-A is an important centromeric protein that ensures a normal mitotic division. Ranks Histone H3 in the nucleosomechromatin at kinetochore level, so it’s implicated in the correct chromosomal segregation and distribution during the phases of mitosis.

Medical Utility

This protein allows to know more thoroughly mitosis, and that such an

accurate distribution of chromosomes in the process is given.

CENP-A is an important centromeric protein that ensures a normal mitotic division. Ranks Histone H3 in the nucleosomechromatin at kinetochore level, so it’s implicated in the correct chromosomal segregation and distribution during the phases of mitosis.

Medical Utility

CENP-A is a protein with wich oneyou can differentiate centromeric

DNA of another parts of thechromosome

The CS, even though it ‘s a little known disease, can provide

important information about autism because it’s highly related to this pathology

Medical Utility

The SLC9A6 gene on Xq26.3 encodes the

Na+/H+ exchanger, NHE6. This testing is useful to confirm the diagnosis and to

identify the disease causing mutation within a family to allow for carrier testing and

prenatal diagnosis.

The CS, even though it ‘s a little known disease, can provide

important information about autism because it’s highly related to this pathology

Medical Utility

"We can now study these different mutations and learn how this protein works by how it gets inactivated," he said. "All the different ways it gets inactivated can actually inform us about the different components of the protein that have an important function."

• W H I T E H E A D I N S T I T U T E F O R B I O M E D I C A L R E S E A R C H .

" F A I T H F U L C E L L D I V I S I O N R E Q U I R E S T I G H T L Y C O N T R O L L E D P R O T E I N P L A C E M E N T A T T H E C E N T R O M E R E S . " S C I E N C E D A I L Y . S C I E N C E D A I L Y , 1 7 J U L Y 2 0 1 4 . < W W W . S C I E N C E D A I L Y . C O M / R E L E A S E S / 2 0 1 4 / 0 7 / 1 4 0 7 1 7 1 2 4 5 1 7 .H T M > .

• B R O W N U N I V E R S I T Y . " D I A G N O S T I C C R I T E R I A F O R C H R I S T I A N S O N S Y N D R O M E . " S C I E N C E D A I L Y . S C I E N C E D A I L Y , 2 1 J U L Y 2 0 1 4 . < W W W . S C I E N C E D A I L Y . C O M / R E L E A S E S / 2 0 1 4 / 0 7 / 1 4 0 7 2 1 1 0 0 4 1 6. H T M > .

BIBLIOGRAPHY

GRACIAS!!!

Faithful cell division requires tightly controlled protein placement

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