CNIO researchers delve into the behavior of cohesins

Oct 18, 2013
Cells lacking Pds5B divide their genetic material in a defective manner (right), compared to normal cells (left). Credit: CNIO

Cohesins are protein complexes that join the two copies of each chromosome—called sister chromatids—to ensure that they are shared fairly between the daughter cells during cell division. In this way, each daughter cell receives exactly the same genetic information from the parent cell.

Pds5 is a protein associated with cohesins; it binds cohesins along different chromosome regions. In vertebrates there are two variants of Pds5, Pds5A and Pds5B, not very well characterised to date. Scientists from the Spanish National Cancer Research Centre (CNIO), led by Ana Losada, from the Chromosome Dynamics Group, have discovered—by using genetically-modified mice (knock-out mice for Pds5A and Pds5B)— that the two Pds5 variants are not equivalent, as both are necessary for cell proliferation and for embryo development to take place correctly.

The results, published today in the online version of The EMBO Journal, contribute to improving our understanding of how Pds5 proteins modulate the behaviour of cohesins, either by stabilising or destabilising the binding of cohesins to the chromosomes.

Clinical implications of the study

Illnesses such as Cornella de Lange Syndrome, which affects 1/30,000 newborns and which is characterised by serious physical abnormalities and cognitive impairments, have their origin in the abnormal function of cohesins. Cohesin mutations have recently been identified in some types of tumours, such as bladder cancer or (AML). "If we understand the function and regulation of the cohesins, we can improve the diagnosis and treatment for affected patients", says Losada.

"In this context, we have seen that both forms of Pds5 stabilise the binding of cohesins to the arms and distal regions of chromosomes, whilst only Pds5B does so in the centromeres— the chromosomal regions that are most critical for chromosome separation during ", explains Losada.

But Pds5 proteins not only stabilise cohesins, they can also have the opposite effect when they bind to the Wapl . "In this case, Pds5 contributes to destabilising the binding of cohesins to , which can sometimes be important for activating essential genes at the right moment, as well as for allowing an efficient separation of the sister chromatids during cell division".

Explore further: Dampened mTOR signaling linked with the developmental disorder Roberts syndrome

More information: Pds5B is required for cohesion establishment and Aurora B accumulation at centromeres. Carretero M, Ruiz-Torres M, Rodríguez-Corsino M, Barthelemy I, Losada A. The EMBO Journal (2013). DOI: 10.1038/emboj.2013.230

Journal reference: EMBO Journal search and more info website

Provided by Centro Nacional de Investigaciones Oncologicas (CNIO)

5 /5 (1 vote)
add to favorites email to friend print save as pdf

Related Stories

Chromosome 'glue' surprises scientists

May 06, 2010

Proteins called cohesins ensure that newly copied chromosomes bind together, separate correctly during cell division, and are repaired efficiently after DNA damage. Scientists at the Carnegie Institution have found for the ...

Non-infiltrating bladder cancer exome sequenced

Oct 13, 2013

Bladder cancer represents a serious public health problem in many countries, especially in Spain, where 11,200 new cases are recorded every year, one of the highest rates in the world. The majority of these ...

Mutations in cancer often affect the X chromosome

Oct 18, 2013

Every case of cancer originates from changes in a person's genetic material (mutations). These usually occur as "somatic mutations" in individual cells during an individual's lifetime, rather than being inherited from a person's ...

Recommended for you

Researchers successfully clone adult human stem cells

17 hours ago

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

Researchers develop new model of cellular movement

20 hours ago

(Phys.org) —Cell movement plays an important role in a host of biological functions from embryonic development to repairing wounded tissue. It also enables cancer cells to break free from their sites of ...

For resetting circadian rhythms, neural cooperation is key

Apr 17, 2014

Fruit flies are pretty predictable when it comes to scheduling their days, with peaks of activity at dawn and dusk and rest times in between. Now, researchers reporting in the Cell Press journal Cell Reports on April 17th h ...

User comments : 0

More news stories

Researchers successfully clone adult human stem cells

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

Male monkey filmed caring for dying mate (w/ Video)

(Phys.org) —The incident was captured by Dr Bruna Bezerra and colleagues in the Atlantic Forest in the Northeast of Brazil.  Dr Bezerra is a Research Associate at the University of Bristol and a Professor ...

Researchers develop new model of cellular movement

(Phys.org) —Cell movement plays an important role in a host of biological functions from embryonic development to repairing wounded tissue. It also enables cancer cells to break free from their sites of ...

Impact glass stores biodata for millions of years

(Phys.org) —Bits of plant life encapsulated in molten glass by asteroid and comet impacts millions of years ago give geologists information about climate and life forms on the ancient Earth. Scientists ...