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Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
CLICK ON weeks 0 - 40 and follow along every 2 weeks of fetal development
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Home | Pregnancy Timeline | News Alerts |News Archive Oct 22, 2013

 

Normal cell division (left). Defectively dividing chromosomes without Pds5B (right),

Image Credit: CNIO: Centro Nacional de Investigasiones Oncologicas



Mitosis: cell division producing all body tissues.
Meiosis: cell division producing sex cells only: egg or sperm.







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Cohesins + Pds5 protein = split chromosomes

Pds5 proteins modify cohesins ensuring the precise pulling apart of chromosomes during cell division. Understanding how cohesins are regulated can improve diagnosis and treatment for those with Cornella de Lange Syndrome and for some cancers.

Cornella de Lange Syndrome affects 1/30,000 newborns and is characterised by serious physical abnormalities and cognitive impairments. It originates from the abnormal function of cohesins. Cohesin mutations have also recently been identified in some cancers such as bladder cancer and acute myeloid leukaemia (AML).

Cohesins are protein complexes that separate each chromosome—called sister chromatids—to ensure they are shared eually between the two daughter cells produced through MITOSIS or cell division leading to body development. Each daughter cell must receive exactly the same genetic information from each parent cell to ensure cell health.


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 — but neither is well characterised as yet.


Scientists from the Spanish National Cancer Research Centre (CNIO), led by Ana Losada, from the Chromosome Dynamics Group, have discovered—using genetically-modified mice — that the two Pds5 variants are not equivalent. But, both are necessary for cell proliferation and for embryo development to take place correctly.

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


"If we understand the function and regulation of the cohesins, we can improve the diagnosis and treatment for affected patients.

"We have seen that both forms of Pds5 stabilise the binding of cohesins to the arms and distal regions of chromosomes, while only Pds5B does so in the centromeres— the chromosomal regions that are most critical for chromosome separation during cell division."

Ana Losada, PhD, leader, Chromosome Dynamics Group, CNIO: Centro Nacional de Investigasiones Oncologicas or Spanish National Cancer Research Centre


Pds5 proteins not only stabilise cohesins, they can also have the opposite effect when they bind to the Wapl protein.

Losada explains: "In this case, Pds5 contributes to destabilising the binding of cohesins to chromosomes, 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."

Abstract
Cohesin mediates sister chromatid cohesion and contributes to the organization of interphase chromatin through DNA looping. In vertebrate somatic cells, cohesin consists of Smc1, Smc3, Rad21, and either SA1 or SA2. Three additional factors Pds5, Wapl, and Sororin bind to cohesin and modulate its dynamic association with chromatin. There are two Pds5 proteins in vertebrates, Pds5A and Pds5B, but their functional specificity remains unclear. Here, we demonstrate that Pds5 proteins are essential for cohesion establishment by allowing Smc3 acetylation by the cohesin acetyl transferases (CoATs) Esco1/2 and binding of Sororin. While both proteins contribute to telomere and arm cohesion, Pds5B is specifically required for centromeric cohesion. Furthermore, reduced accumulation of Aurora B at the inner centromere region in cells lacking Pds5B impairs its error correction function, promoting chromosome mis-segregation and aneuploidy. Our work supports a model in which the composition and function of cohesin complexes differs between different chromosomal regions.


Reference article:
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

Original press releas:http://www.eurekalert.org/pub_releases/2013-10/embl-co101113.php