Proofreading protein

4 September 2008

Scientists from the Structural Genomics Consortium have determined the three dimensional structure of a key protein component involved in enabling ‘epigenetic code’ to be copied accurately from cell to cell.

Epigenetic code is a series of chemical switches added on to DNA to ensure that body cells can form different types of tissue, despite having identical DNA code.

It is essential that the epigenetic code is copied accurately when DNA is copied from cell to cell, as a breakdown in this system might mean that a gene for cell growth is accidentally switched on, for example, leading to unregulated cell growth and the development of tumours.

Research published in 2007 showed the importance of the nuclear protein UHRF1 in ensuring that the epigenetic code is accurately copied. The key element of UHRF1 involved in this ‘proofreading’ process is known as the Set and Ring Associated (SRA) domain. Now, three papers published in Nature have revealed the mechanisms by which this domain accomplishes this task.

A co-author of one of the papers, Professor Sirano Dhe-Paganon from the Structural Genomics Consortium laboratories at the University of Toronto, Canada, says: “Given the increasing focus on epigenetics as a mechanism behind cancer, elucidating the structure of UHRF1 may provide crucial insights into what goes wrong.”

Avvakumov GV et al. Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1. Nature 2008 [Epub ahead of print].