Navigation Links
Enzyme crystal structure reveals 'unexpected' genome repair functions

The study is being published in an advance online version of the journal Molecular Cell.

The research looked at XPB helicase from an archaea, a single cell organism similar to bacteria. Helicases are enzymes that unwind or separate the strands of the nucleic acid double helix, an action that is critical to transcription and nucleotide excision repair (NER), as well as other cell processes.

"XPB was initially identified as the gene responsible for NER defects in xeroderma pigmentosum patients, who are hypersensitive to light and have a dramatically increased risk of skin cancer," says John A. Tainer, a professor at Scripps Research and its Skaggs Institute for Chemical Biology who led the study. "This reflects the fact that XPB plays a key role in unwinding damaged DNA during NER, which removes a broad spectrum of DNA lesions, including those caused by exposure to ultraviolet light."

DNA needs constant repair because of the damage from a variety of sources that occurs to its base pairs of nucleotides. It is estimated that in every human cell more than 10,000 DNA bases are repaired each day, making NER critically important for cell survival and protection against mutations. NER is a critical defense mechanism that removes DNA lesions caused by the mutating effects of sunlight (ultraviolet light) and toxic chemicals.

In addition, NER is critical to the success of the anticancer drug cisplatin, since cisplatin works by initiating the process of DNA repair, in turn activating apoptosis or programmed cell death when the repair process fails. "Because chemotherapeutic agents like the chemotherapy drug cisplatin and radiation therapy work by essentially damaging DNA, any new understanding of the DNA repair mechanism could mean potential improvements in the treatment of cancer," Tainer says.

Prior to this study, there were no specific models for how XPB acts in DNA separation either to initiate transcription or to begin NER. There we re also no models for the role that XPB, which is an essential subunit of Transcription Factor IIH (TFIIH) functional assembly complex, might play in changing conformations for TFIIH's alternate roles in either transcription or DNA repair.

The XPB crystal structures developed by the researchers identified unexpected functional domains for XPB that, according to the study, help "address key questions about XPB structure-function relationships for transcription and nucleotide excision repair."

Research Associate Li Fan of Scripps Research, the first author of the study, adds, "We were surprised when we found that XPB contains a domain structurally similar to the mismatch recognition domain of a bacterial DNA repair protein MutS. MutS helps recognize and repair mismatched DNA in E. coli. These two proteins have little sequence similarity. Biochemical assays following this discovery indicate that this domain allows XPB to interact with damaged DNA and enhances its unwinding activity on damaged DNA."

The report suggests that unknown protein and DNA interactions at transcription sites activate XPB within the TFIIH complex to allow it to start the DNA unwinding process.

"Even though TFIIH does not act directly in initial damage recognition, the interaction of XPB with the DNA lesion suggests that XPB plays a role in switching TFIIH from transcription mode to NER," Tainer says. "The structural biochemistry of XPB that we discovered shows an unexpected molecular mechanism by which XPB plays a key role in determining exactly how TFIIH functions, whether in transcription or repair mode."


'"/>

Source:Scripps Research Institute


Related biology news :

1. Enzyme, lost in most mammals, is shown to protect against UV-induced skin cancer
2. Novel Enzyme Shows Potential As An Anti-HIV Target
3. Enzyme allows B cells to resist death, leading to leukemia
4. Enzyme shown to help protect genomic stability
5. Measuring Enzymes At End Of Cancer Pathway Predicts Outcome Of Tarceva, Taxol
6. Enzymes newly discovered role may make it target for arthritis treatment
7. Promiscuous Catalytic Activity Possessed by Novel Enzyme Structure
8. Gene Bridges And Covalys To Develop Restriction-Enzyme-Free SNAP-tag Gene Fusion Kits
9. Newly Discovered Role for Heart Response Enzyme May Yield Better Heart Failure Therapy
10. Enzyme affects hypertension by controlling salt levels in body
11. Enzyme inhibitors block replication of SARS virus
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:12/2/2016)... , Dec. 1, 2016   SoftServe ... announced BioLock , an electrocardiogram (ECG) biosensor ... monitoring, a key IoT asset. The smart system ... a vehicle,s steering wheel and mobile devices to ... touch. As vehicle technology advances, so ...
(Date:11/29/2016)... Nearly one billion matches per second with DERMALOG,s high-speed AFIS    ... ... DERMALOG is Germany's largest Multi-Biometric supplier: The company's ... Systems) ... largest Multi-Biometric supplier: The company's Fingerprint Identification System is part of an ...
(Date:11/21/2016)...   Neurotechnology , a provider of high-precision ... that the MegaMatcher On Card fingerprint matching algorithm ... NIST Minutiae Interoperability Exchange (MINEX) III ... of the evaluation protocol. The ... fingerprint templates used to establish compliance of template ...
Breaking Biology News(10 mins):
(Date:12/2/2016)... N.Y. , Dec. 2, 2016 More than ... (CSHL) 11th Double Helix Medals dinner ( DHMD ). The gala was ... New York City and honored ... their contributions, respectively, to health and medicine and the public ... Ali in 2006, the event has raised $40 million ...
(Date:12/2/2016)... Calif. , Dec. 2, 2016 Amgen (NASDAQ: ... AGN ) today announced the submission of a Marketing Authorization ... 215, a biosimilar candidate to Avastin ® (bevacizumab). The ... submitted to the EMA. "The submission of ... Amgen seeks to expand our oncology portfolio," said Sean ...
(Date:12/2/2016)... Research and Markets has announced the addition of ... to their offering. ... , , An ... is anticipated. Nanotechnology will be applied at all stages of ... applications in clinical trials. Many of the assays based on ...
(Date:12/2/2016)... ... December 01, 2016 , ... ... the value of DNA microarray comparative genomic hybridization (array CGH) for HER2 ... Cancer Symposium. Using molecular test results from tumors with previously documented positive, ...
Breaking Biology Technology: