Navigation Links
DNA Repair Proteins Monitored at Double-strand Break

Investigators at St. Jude Children's Research Hospital had a molecules eye view of the human cells DNA repair kit as it assembled on a double-strand break to link together the broken ends. Double-strand breaks are ruptures that cut completely across the twisted, ladder-like structure of DNA, breaking it into two pieces.

Using a technique developed specifically for this project, the St. Jude researchers could determine when repair proteins arrived at or around the DNA break and evaluate its repaireven when particular proteins shifted away from the break to make room for others. A report on this work appears in the May 7 online issue of "Nature Cell Biology."

The findings are important because disruption of the precise movement of these repair proteins can cause mutations, cell death or cancer, and the ability to track the process so closely will give researchers critical insights into what can go wrong with DNA repair. This could lead to novel ways to make cancer cells more sensitive to therapy by blocking their ability to repair double-stranded breaks caused by chemotherapy or radiation. It could also suggest new strategies for enhancing repair of double-stranded DNA caused by radiation, natural oxidants in food or the body and other toxins that can cause disease and aging.

"Prior to this work, there was no practical and efficient way to find and study the DNA repair proteins that organize themselves on and around a double-strand break in human cells," said Michael Kastan, M.D., Ph.D., St. Jude Cancer Center director. "Our approach solved that problem and allowed us to document the cells response to double-strand DNA breaks over time. The technique provides significantly more information about the proteins that repair DNA than is possible using the standard microscope-based approach previously used for such work." Kastan is the papers senior author.

A deficiency in two of these repair proteins, ATM and NBS1, l eads to defects in double-strand break repair by disrupting the signaling processes triggered by the break.

"A lack of functioning ATM causes ataxia-teleangiectasia, a disease that causes a variety of debilitating problems, such as neurodegeneration, cancer and sensitivity to irradiation leading to double-strand breaks that are not repaired," Kastan said.

"And a lack of NBS1 causes Nijmegen breakage syndrome, another disease that leaves its victims at high risk for cancer and higher sensitivity to DNA-damaging radiation. So this work has important medical implications for these and other diseases linked to disruption of double-strand break repair."

The assay, developed by Elijahu Berkovich, Ph.D., in Kastans laboratory, demonstrates how key repair proteins, such as ATM, NBS1, XRCC4 and gamma-H2AX, interact to coordinate repair of double-strand breaks. For example, the investigators showed that NBS1 recruits ATM to the break; and that ATM and NBS1 cooperate to disrupt nucleosomesthe compact packages formed when strands of DNA wind around proteins, called histones, like thread around a spool.

Disruption of the nucleosome at the site of a double-strand break allows the DNA to unravel and expose the area to repair proteins; the loss of functioning ATM and NBS1 blocks this important process. The team also showed that both NBS1 and ATM are needed to ensure that the repair factor, XRCC4, arrives at the double-strand break to help repair the damage.


'"/>




Related medicine news :

1. Brain Cell Repair Loss disclosed
2. Stem Cells To Repair Heart Damage
3. Predictors Of Wound Infection In Ventral Hernia Repair
4. Stem Cells From Hair Follicle To Repair Nerve Damage
5. Little Known DNA Repair Enzyme May Be A Tumor Suppressor Gene
6. Muscle Derived Stem Cell Can Repair Damaged Cartilage
7. Unchecked Cellular Repair Pathway Causes Liver Cancer
8. Bone Marrow Cells Aid In Heart Repair
9. Heart Attack Damage Repaired with Stem cells
10. Pig Stem Cells Show Promise in Repairing Animals’ Heart Attack Damag
11. Stem Cells In Brain Have Potential For Sensing Damage And To Repair
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/27/2017)... ... March 27, 2017 , ... American Veterinarian™, the ... on veterinary medicine, announces the launch of Veterinarian’s Money Digest™, a business and ... April edition of American Veterinarian™. , “We look forward to launching ...
(Date:3/27/2017)... ... March 27, 2017 , ... EpiGentek , a Farmingdale, ... recent RNA methylation “gold rush” with their established portfolio of optimized assay kits ... N6-methyladenosine, or m6A , RNA methylation has received a new burst in ...
(Date:3/27/2017)... ... 27, 2017 , ... According to the American Cancer Society , the ... than 95%. Once the cancer spreads to other organs, bones, or lymph nodes, however, ... to avoid this latter group, tune in to Lifestyle Magazine on April ...
(Date:3/27/2017)... ... March 27, 2017 , ... ?Grow Healthy ... resolve the pending litigation between itself and 1800 Vending DBA Healthy You Vending. ... “I am thrilled to announce that we have now reached a settlement agreement ...
(Date:3/27/2017)... ... March 27, 2017 , ... Harris Communications, Inc., a leading ... bringing its latest products to the Deaf Seniors of America Conference, April 4-7 at ... to meet with knowledgeable ASL friendly staff from Harris Communications and to try out ...
Breaking Medicine News(10 mins):
(Date:3/24/2017)... PUNE, India , March 24, 2017 Abdominal Aortic ... reach $2,614 million by 2022, Globally, registering a CAGR of 5.1% from 2016 to ... and is projected to dominate the market during the study period. ... ... ...
(Date:3/24/2017)... , March 24, 2017  Zymo Research ... and Hamilton Robotics, Inc., who designs, manufactures ... ongoing collaboration that teams Zymo Research,s DNA ... and DNA extraction products with Hamilton,s high-throughput ... optimized methods for microbiomics and RNA isolation ...
(Date:3/24/2017)... Research and Markets has announced the addition of the "Dental ... ... markets for Dental Implants in US$ Million. The report provides separate comprehensive ... , Europe , Asia-Pacific , ... Annual estimates and forecasts are provided for the period 2015 through ...
Breaking Medicine Technology: