Navigation Links
Newly identified proteins critical to FA pathway DNA repair function
Date:3/25/2010

CINCINNATI Identification of two new proteins in the Fanconi anemia DNA repair pathway may help explain genetic instability in people with Fanconi anemia and how otherwise healthy people are susceptible to cancer from environmentally triggered DNA damage.

A study in the March 26 Molecular Cell adds another layer of complexity to the multifaceted Fanconi anemia (FA) pathway. The research was led by scientists in the division of Experimental Hematology and Cancer Biology at Cincinnati Children's Hospital Medical Center.

Mounting scientific evidence suggests the FA repair pathway is necessary to limit genomic instability caused by abnormal structural changes during DNA replication and cell division. In some people the pathway is genetically unstable, putting them at risk for the Fanconi anemia blood disorder, physical defects and possibly cancer.

"Although only a small number of people have Fanconi anemia, this study helps us explain the very intricate steps that occur during DNA repair processes and how defects in DNA repair processes can lead to cancer in the general population," said Amom Ruhikanta Meetei, Ph.D., senior investigator on the study.

The researchers show how the two novel proteins which they named MHF1 and MHF2 work together to bind to specific DNA structures and are "indispensable for the functional integrity of the FA pathway." The proteins were identified working through a specific core component protein of the FA pathway called FANCM, one of eight currently known to make up the FA core complex.

FA cells are extremely sensitive to exposure from agents that can cause DNA interstrand crosslinks (ICLs), abnormal structures that block DNA replication. When disruptions from environmental factors or inherent genetic instability create the possibility for ICLs, the study shows that MHF1 and MHF2 help FANCM prevent or repair these crosslinks, which if unresolved can lead to cell defects and disease

The researchers also report that loss of MHF1 alone disrupts normal function of the entire FA pathway. In fact, when the researchers suppressed MHF1, it destabilized FANCM and caused increased chromosome aberrations after exposure to capothecin, an agent that causes ICLs.

As they move forward with their research, the investigators next want to analyze cells from people who have Fanconi anemia to see if they detect mutations in MHF1 or MHF2 that could help explain genetic instability in these patients, said Thiyam Ramsing Singh, Ph.D., first author on the study and a member of Dr. Meetei's laboratory.

The precise molecular functions of the FA pathway and how they influence the development of cancers are still being uncovered. The identification of FANCM as part of the FA core complex and its DNA repair function was an important step forward, and was first reported in 2005 by Dr. Meetei and his research colleagues.


'/>"/>

Contact: Nick Miller
nicholas.miller@cchmc.org
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

Related medicine news :

1. Newly discovered mechanism by which blood clots form
2. MIT is pleased to announce the nomination of Mr. Jacques Gauthier and Mr. Michel Carrier to its newly formed Advisory Board
3. The Newly Renamed Resource Center of Somerset Names John Graf, Jr. Director of Development
4. Newly Identified Gene Variants Linked to Diabetes
5. Newly identified genes influence insulin and glucose regulation
6. Research confirms efficacy of the newly reclassified TMN staging system
7. Independence Blue Cross Names John Janney to Newly Created Position: Senior Vice President Marketing Services
8. Beat The Odds and Get Back on Track; Revitalizing Fitness Training and Exercise Resolutions With Newly Released, Complimentary Video Series
9. Gene discovered for newly recognized disease in Amish children
10. Possible pharmacological target(s) identified in pediatric OSA
11. 3 key factors to help children avoid social rejection identified
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/5/2016)... ... May 05, 2016 , ... MAP ... Platform, announced today that Enlightened Solutions has joined the Premier Outcomes-Driven Provider Network. ... care continuum for their patients being treated for substance use. , Enlightened Solutions ...
(Date:5/5/2016)... ... May 05, 2016 , ... Linfield College Online and Continuing Education ... by waiving the $50 application fee for all qualified applicants from May 1–14. Students ... Waiver option when applying . , With the RN to BSN ...
(Date:5/5/2016)... ... , ... Augusta Public Schools has teamed with CareDox to provide confidential and ... offices to streamline and bolster care for district students. , Augusta School District, ... schools serve 2,300 students among its six schools. , Monica Guilliams, BSN, RN, ...
(Date:5/5/2016)... ... May 05, 2016 , ... BloodHub, the ... and service orders. Blood suppliers and their hospitals use BloodHub for order ... 13,000 active users across 2,100 hospitals who use our platform to processes thousands ...
(Date:5/4/2016)... ... , ... ProList is a set of 30 self-animating bullet points created for ... easily create lists for presentations, youtube productions, and more. Simply choose from ProList’s ... perfect complement to presentation style videos. , ProList is a package of 30 self-animating ...
Breaking Medicine News(10 mins):
(Date:5/4/2016)... -- According to market research "Global Computed Tomography ... 2022 - Industry Insights by Slice Type (High, Mid and ... P&S Market Research, the global computed tomography market ... expected to grow at a CAGR of 5.0% during 2016-2022. ... expected to witness the faster growth, CAGR of 5.3%, during ...
(Date:5/4/2016)... New Jersey , May 4, 2016 ... its successful completion of an alternative public offering (APO). ... wholly owned operating company, Valeritas, Inc. and a private ... common stock at $5.00 per share. Under ... on May 3, 2016, Valeritas Holdings, Inc. will trade ...
(Date:5/4/2016)... Research and Markets has ... Myeloid Leukemia Market and Competitive Landscape Highlights ...      (Logo: http://photos.prnewswire.com/prnh/20160330/349511LOGO ) ... Competitive Landscape Highlights 2016, provides comprehensive insights ... Myeloid Leukemia epidemiology, Acute Myeloid Leukemia market ...
Breaking Medicine Technology: