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:3/31/2016)...  Genomics firm Nabsys has completed a financial  restructuring ... , M.D., who returned to the company in October ... team, including Chief Technology Officer, John Oliver , ... and Vice President of Software and Informatics, Michael ... Dr. Bready served as CEO of Nabsys from 2005-2014 ...
(Date:3/21/2016)... March 22, 2016 Unique ... passcodes for superior security   ... provider of secure digital communications services, today announced it ... and offer enterprise customers, particularly those in the Financial ... and voice authentication within a mobile app, alongside, and ...
(Date:3/14/2016)... March 14, 2016 NXTD ) ("NXT-ID" ... commerce market, announces the airing of a new series of ... week of March 21 st .  The commercials will air ... popular Squawk on the Street show. --> NXTD ... growing mobile commerce market, announces the airing of a new ...
Breaking Biology News(10 mins):
(Date:5/5/2016)... ... May 05, 2016 , ... American Process, Inc. ... patents, U.S. Patent Nos. 9,322,133 and 9,322,134, to API and its affiliated companies ... well as hydrophobic nanocellulose compositions. In addition to these patents and U.S. ...
(Date:5/4/2016)... ... May 04, 2016 , ... ... further than LaJollaCooks4u, San Diego’s premiere hands-on cooking experience. Offering everything from gourmet ... mom an experience she won’t forget. , Guests that visit LaJollaCooks4u share an ...
(Date:5/4/2016)... May 4, 2016 According to ... "Metabolomics Market - Global Industry Analysis, Size, Share, Growth, ... is anticipated to expand at a CAGR of 17.1% ... by 2024. Metabolomics is the extensive study ... biofluids, tissues or organisms. Together, these small molecules and ...
(Date:5/3/2016)... ... May 03, 2016 , ... Morf Media Inc ... training platform on mobile devices, today released a new interactive Food and ... Devices. The course is essential for owners or operators of places of business ...
Breaking Biology Technology: