Newly identified proteins critical to FA pathway DNA repair function

Mar 25, 2010

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 (FA) pathway. The research was led by scientists in the division of Experimental 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 and cell division. In some people the pathway is genetically unstable, putting them at risk for the Fanconi anemia , 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 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 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.

Explore further: Fighting bacteria—with viruses

add to favorites email to friend print save as pdf

Related Stories

Two proteins act as molecular tailors in DNA repair

Nov 13, 2009

(PhysOrg.com) -- On average, our cells encounter a very lethal form of DNA damage 10 times a day. Lucky for us, we have the capacity to repair each and every one of them. New research now reveals exactly how two well-known ...

Recommended for you

Fighting bacteria—with viruses

19 hours ago

Research published today in PLOS Pathogens reveals how viruses called bacteriophages destroy the bacterium Clostridium difficile (C. diff), which is becoming a serious problem in hospitals and healthcare institutes, due to its re ...

Atomic structure of key muscle component revealed

20 hours ago

Actin is the most abundant protein in the body, and when you look more closely at its fundamental role in life, it's easy to see why. It is the basis of most movement in the body, and all cells and components ...

Brand new technology detects probiotic organisms in food

Jul 23, 2014

In the food industr, ity is very important to ensure the quality and safety of products consumed by the population to improve their properties and reduce foodborne illness. Therefore, a team of Mexican researchers ...

Protein evolution follows a modular principle

Jul 23, 2014

Proteins impart shape and stability to cells, drive metabolic processes and transmit signals. To perform these manifold tasks, they fold into complex three-dimensional shapes. Scientists at the Max Planck ...

Report on viruses looks beyond disease

Jul 22, 2014

In contrast to their negative reputation as disease causing agents, some viruses can perform crucial biological and evolutionary functions that help to shape the world we live in today, according to a new report by the American ...

User comments : 0