Navigation Links
Abnormal DNA maintenance related to cancer
Date:12/10/2012

DNA, like houses and cars, needs ongoing maintenance. Rays of ultraviolet sunlight, chemical pollutants and normal biochemical processes in the cell can damage it. Cells routinely repair this damage before making proteins or copying DNA for cell division. The repairs are remarkably accurate in normal cells but cancer cells make far more mistakes in fixing their DNA. Alan Tomkinson, PhD, University of New Mexico Professor of Internal Medicine and Associate Director of Basic Research at the UNM Cancer Center, wants to understand why and how these repair mechanisms go awry in cancer cells. This understanding could lead to new targets for cancer drugs. Dr. Tomkinson recently won a 4-year $1 million grant renewal to continue his 18-year research investigation on DNA ligases, the enzymes that repair DNA strands.

DNA ligases fuse the backbone of a DNA strand. The strand is a long string of nucleotides that structurally resembles one half of a ladder sliced lengthwise through the rungs. Each nucleotide consists of a deoxyribose molecule with a phosphate molecule on one side and a base molecule on another. The phosphate of one nucleotide attaches to the deoxyribose of the adjacent nucleotide, forming the alternating phosphate-deoxyribose DNA strand backbonethe side of the ladder. In a DNA moleculea full laddereach base attaches to a complementary base on the mirror strand to form the rung-like structures that encode genes.

Products of normal cellular chemical reactions and DNA repair proteins that replace damaged bases can break the phosphate-deoxyribose backbone. If only one strand is broken, the overall DNA structure remains intact because the bases of the broken strand still attach to those of the second, unbroken strand. It is relatively simple for DNA ligases to fuse such single-strand breaks. The DNA molecule falls apart, however, if both strands are broken at the same time and in the same place. In this situation, the cell has several different options to repair these breaks, all of which end with a DNA ligase rejoining the DNA backbone. Dr. Tomkinson studies how DNA ligases work with other DNA repair proteins to repair damage to DNA.

These repair mechanisms are not perfect, though. "You can measure the frequency at which the cell will make a mistake," says Dr. Tomkinson. This error rate is very low in normal cells but the DNA of cancer cells has many changes. "The error rate is so low in normal cells that you would not expect to see cancer normally," says Dr. Tomkinson. "In the process of a normal cell turning into a cancer cell," he explains, "a certain number of changes must accumulate. So at some stage it appears that the mechanisms that normally repair DNA become abnormal."

In fact, these processes become so abnormal that DNA in cancer cells is vastly different from DNA in normal cells. Normal cells have 46 chromosomes; cancer cells frequently do not, a condition called aneuploidy. Normal cells have 23 pairs of chromosomes and the chromosomes of 22 of those pairs resemble each other. Cancer cells, in contrast, have many chromosomes that look vastly different and researchers can see these differences through modern staining techniques that allow them to stain each chromosome a different color. In normal cells, the chromosome pairs retain their color and stay monochromatic; cancer cells become multicolored because the cell links part of one chromosome to part of another. Called translocation, this shuffling of DNA pieces is common in some cancers. "A lot of leukemias have single translocations and they're stable events that you can see easily by cytogenetics," says Dr. Tomkinson. "In some breast cancers you see almost a complete shuffling of the genetic information. The chromosomes look more like a rainbow than like a single color and the sizes are mismatched."

So, Dr. Tomkinson is studying the enzymes that complete the repair of DNA, the DNA ligases, to learn how the process becomes abnormal. Humans have three types of DNA ligases named ligase I, ligase III, and ligase IV. Dr. Tomkinson is able to measure each ligase's activities in a cell. He has found that the type of ligase that is most active differs between a normal cell and a cancer cell. Normal cells have more ligase IV activity while cancer cells have more ligase III activity. Dr. Tomkinson's grant renewal will further investigate what each of these ligases do and how their activity differs between normal and cancerous cells. "If you know that cancer cells have an abnormality in how they handle DNA damage," he says, "you can selectively target that abnormality so that you kill the cancer cell without harming normal cells."


'/>"/>

Contact: Michele Sequeira
MSequeira@salud.unm.edu
505-925-0486
University of New Mexico Cancer Center
Source:Eurekalert

Related medicine news :

1. Documenting womens experiences with chromosome abnormalities found in new prenatal test
2. Abnormal carotid arteries found in children with kidney disease
3. Double drug combo could shut down abnormal blood vessel growth that feeds disease
4. Brain Scans of Hoarders Show Unique Abnormalities
5. Gene Mutation Linked to Facial, Skull Abnormalities
6. Myelodysplastic Syndrome Linked to Abnormal Stem Cells
7. Genome-wide analysis shows previously undetected abnormalities in parents of affected children
8. Abnormal gene product associated with prostate cancer generated by unusual mechanism
9. Treatment of childhood OSA reverses brain abnormalities
10. Genetic abnormalities in benign or malignant tissues predict relapse of prostate cancer
11. Insecticide Linked to Brain Abnormalities in Kids
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:8/16/2017)... ... August 16, 2017 , ... Paul Vitenas, MD, FACS , ... Top Doctor. The annual list identifies the nation’s top physicians, in a variety of ... it to the top of Castle Connolly’s coveted ranking. , Castle Connolly is the ...
(Date:8/16/2017)... (PRWEB) , ... August 16, 2017 , ... A global ... has successfully opened clubfoot clinics in all 29 Indian states—bringing the country one step ... in Kangra, Himachal Pradesh, the nonprofit organization is on track to enroll 10,000 children ...
(Date:8/16/2017)... ... August 16, 2017 , ... ... the endoscope after every reprocessing cycle, both between patient procedures and before storage, ... infections. Drying is as important to the prevention of disease transmission and nosocomial ...
(Date:8/16/2017)... ... August 16, 2017 , ... Fusion Flix Inc., a ... programming over four countries and millions of viewers in a partnership with the Amazon ... buy On-Demand and fully available on Blu Ray disc in 2018. Proceeds will be ...
(Date:8/16/2017)... ... August 16, 2017 , ... ... eBook, 9781498499620    ) shares that during the time of a cancer diagnosis, surgery and ... God's love, and all the many ways God shows love to those who ...
Breaking Medicine News(10 mins):
(Date:8/8/2017)...  BioLineRx Ltd. (NASDAQ/TASE: BLRX), a clinical-stage biopharmaceutical company ... results for the second quarter ended June 30, 2017. ... 2017 and to date: ... the Company,s lead project, BL-8040: Announced ... as novel stem cell mobilization treatment for autologous bone-marrow ...
(Date:8/7/2017)... -- Diplomat Pharmacy, Inc. (NYSE: DPLO), the nation,s largest independent specialty ... 2017.  All comparisons, unless otherwise noted, are to the quarter ... Second Quarter 2017 Highlights include: ... of 3.5% Total prescriptions dispensed of 220,000, ... versus 7.6% Gross profit per prescription ...
(Date:8/2/2017)... Aug. 2, 2017 Fenita J. ... as a Pinnacle Lifetime Professional in the Field ... Manager at Turing Pharmaceuticals, AG. Her skills and ... relationship building.                ... 25 years of experience as a highly successful ...
Breaking Medicine Technology: