Judging DNA by its cover

Jul 23, 2012

Stem cells hold great promise for the medicine of the future, but they can also be a cause of disease. When these self-renewing, unspecialized cells fail to differentiate into diverse cell types, they can start dividing uncontrollably, leading to cancer. Already several decades ago, Weizmann Institute scientists were among the first to demonstrate the link between cancer and the faulty differentiation of stem cells. Now a new Weizmann Institute-led study, published in Molecular Cell, reveals a potential molecular mechanism behind this link.

The scientists managed to uncover the details of a step in the process of DNA "repackaging" that takes place during embryonic . It turns out that for the cells to differentiate properly, certain pieces of the packaging of their must be labeled by a molecular tag called ubiquitin. Such tagging is required for turning on a group of particularly long , which enable the stem cell to differentiate. The researchers identified two switches: An enzyme called RNF20 enhances the tagging, whereas a second enzyme, USP44, does the opposite, shutting it down. Furthermore, it appears that both these must operate properly for the differentiation process to proceed efficiently. When the scientists interfered with the tagging – either by disabling the "ON" switch RNF20, or by deregulating the activity of the "OFF" switch USP44 – the stem cells failed to differentiate.

These experiments might explain the significance of molecular defects identified in a number of cancers, for example, the abnormally low levels of RNF20 in certain breast and prostate cancers and the excess of USP44 in certain leukemias. Notably, faulty differentiation of is often a hallmark of the more aggressive forms of cancer. This research was led by Prof. Moshe Oren of the Molecular Cell Biology Department, with Prof. Eytan Domany of the Physics of Complex Systems Department and Dr. Jacob Hanna of the Molecular Genetics Department. The team included Weizmann Institute's Gilad Fuchs, Efrat Shema, Rita Vesterman, Eran Kotler, Sylvia Wilder, Lior Golomb, Ariel Pribluda and Ester Feldmesser, as well as Zohar Wolchinsky of the Technion – Israel Institute of Technology, Feng Zhang and Xiaochun Yu of the University of Michigan in the US, Mahmood Haj-Yahya and Ashraf Brik of Ben-Gurion University of the Negev, and Daniel Aberdam of the Technion and the University of Nice-Sophia Antipolis in France.

This study belongs to a relatively new direction in cancer research: Rather than focusing on the genes involved, it highlights the role of epigenetics – that is, processes that do not modify the gene code, itself, but affect the way its information is interpreted within the cell. Understanding the epigenetic roots of cancer will advance the search for effective therapies for this disease.

Explore further: Two-armed control of ATR, a master regulator of the DNA damage checkpoint

add to favorites email to friend print save as pdf

Related Stories

Controlling self-renewal of stem cells

Sep 02, 2011

(PhysOrg.com) -- Scientists from the Friedrich Miescher Institute for Biomedical Research (FMI) are the first to establish a direct link between a conserved stem cell factor and the cell cycle regulation in ...

New study hopeful on neural stem cells

Aug 05, 2006

Neural stem cells derived from federally approved human embryonic cells are inferior to stem cells derived from donated fetal tissue, a new study found.

Identification of a novel neural stem cell type

Jan 14, 2008

As published in the upcoming issue of G&D, sesearchers from the Sloan-Kettering Institute, led by Dr. Lorenz Studer, have discovered a novel type of neural stem cell, which has a broader differentiation potential than previously ...

Recommended for you

Japanese scientist resigns over stem cell scandal

7 hours ago

A researcher embroiled in a fabrication scandal that has rocked Japan's scientific establishment said Friday she would resign after failing to reproduce results of what was once billed as a ground-breaking study on ...

'Hairclip' protein mechanism explained

21 hours ago

Research led by the Teichmann group on the Wellcome Genome Campus has identified a fundamental mechanism for controlling protein function. Published in the journal Science, the discovery has wide-ranging implications for bi ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.