DNA repair processes start with protein tags

	RIKEN Discovery Research Institute Cellular Physiology Laboratory Chief Scientist: Fumio Hanaoka Senior Scientist: Kaoru Sugasawa



DNA repair processes start with protein tags

Sunburns, thankfully, are not permanent. This visible sign of ultra-violet (UV) damage gradually fades away, indicating that damage to our skin's cells is being repaired. Damage inflict by UV exposure can go deep into our cells, into the DNA that is wound tightly in the nucleus of our cells. This damage also needs to be repaired. How DNA damage is quickly found and fixed remained unknown until a collaborative effort led by Fumio Hanaoka at the Cellular Physiology Laboratory in RIKEN Discovery Research Institute. This research team recently shed light on how a combination of proteins find, tag and organise to repair DNA in the May 6^th 2005 issue of Cell. Minor damage along any long track needs to be detected and tagged before it can be repaired. On the railroad, human beings walk along the tracks scanning the rails for bulges, breaks, and weaknesses in a tedious, time consuming process. Once identified, work teams are dispatched to the damaged areas to fix the tracks. Monitors and tags are also employed in living cells to scan for damage and signal repair to DNA. The process working on UV-induced lesions is called nucleotide excision repair (NER). This system operates in two ways. NER proteins can either bind directly to damaged sites and flag down help or engage the transcription machinery when it stumbles upon damage by signalling repair proteins to resume transcription immediately. When DNA is damaged by UV exposure a tagging system initiates repairs using various protein complexes including the Xeroderma pigmentosum group C (XPC) protein complex. XPC binds to lesions in DNA and participates in the seek-and-tag team for DNA repair. Researchers also know that skin and other cancers are more common when this protein complex is impaired or missing suggesting that a malfunction in the repair system increases a cell's vulnerability to abnormal development because DNA is damaged. The role of XPC in this repair seems vital. The team conducted in vivo and in vitro studies to see how XPC and another protein complex, the UV-damaged DNA-binding protein (UV-DDB), locate and tag lesions along the strands. XPC responded to UV irradiation by undergoing a reversible change that formed branching structures by conjugation to a small protein, ubiquitin. Two events must occur before this ubiquitylation can happen. The UV-DDB protein complex must first bind to the damaged site. Once there, it draws the XPC complex to the damaged site where the combined complex is then ubiquitylated. This ubiquitylation changes the DNA-binding properties of both XPC and UV-DDB, thereby letting XPC push the tightly-bound UV-DDB away from the lesion. This done, repairs can begin. When the sun damages our DNA, UV-DDB seeks out that damage and calls XPC to tag the site and bring in the repair crew. This research was published in the 6 May 2005 edition of Cell (Vol. 121, pp.387-400).


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