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Chromatin remodeling complex connected to DNA damage control
Date:8/13/2007

hat wants access to DNA, such as a transcription factor or DNA repair machinery," Shen says.

"Chromatin remodeling shuffles the nucleosomes around to create access to DNA," Shen says. "This moving and sliding of the 'beads on the string' is accomplished by large protein complexes, ATP-dependent chromatin remodeling complexes."

In this case, the Ies4 subunit of the remodeling INO80 complex is phosphorylated by ATM/ATR, a necessary step for certain DNA checkpoints to work properly.

When Shen and colleagues used a mutant version of Ies4 to mimic constant phosphorylation, more cells were stuck in a checkpoint pause, blocking cell division. When phosphorylation was blocked, the cells' response to replication stress was impaired, greatly slowing down replication in the absence of another replication checkpoint factor called Tof1.

Shen discovered the INO80 chromatin remodeling complex as a post-doctoral fellow at the National Institutes of Health. His research focuses on defining its functions and mechanisms. An earlier paper from his lab in Cell showed that INO80 also is involved in DNA damage repair through its connections to a specific phosphorylated histone.

"Modification of histones has been studied for some time, now we are moving to understand the modification of something that modifies histones," Shen says of INO80.

Shen's research is conducted in yeast, but the pathways involved are conserved in all forms of life with complex cellular organization, known as eukaryotes, right on up to humans, Shen notes.


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Contact: Scott Merville
sdmervil@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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