“Currently, I am trying to establish methods to selectively enrich palindromes from the rest of the cellular DNA, which will allow greater sensitivity in the analysis of the palindrome content of cancer cells,” she said. For example, she said, the group has already determined that certain yeast cells that are susceptible to palindrome formation are far more sensitive than normal cells to radiation as well as to compounds often used in the treatment of cancer, such as cisplatin. They hope to learn what events initiate such unstable formations, and this new understanding could lead to novel treatments. The researchers developed technology that will enable them to examine tumors, with the goal of understanding the likelihood of palindrome formation in these tumors, Rattray said.
“Any gene rearrangement is mutagenic, and rearrangements that promote cellular growth, as in cancer, will naturally be favored by selection.” New Technology Identifies and Characterizes Palindromes The group hypothesized that “in cancers that undergo massive rearrangements, the cells are susceptible to palindrome formation, and once formed, the palindrome’s instability leads to further rearrangements, including gene amplification, translocations, and deletions,” Rattray said. However, Rattray said that her group and others have shown that “DNA palindromes are unstable and can lead to genome rearrangements by themselves, further suggesting palindromes could arise not only by sister chromatid fusion, but also by other mechanisms, such as replication errors.” In the McClintock model, having two centromeres leads to further genomic rearrangements. New Hypothesis for Genomic RearrangementĪccording to Rattray, the favored model, originally proposed more than 60 years ago by Barbara McClintock, Ph.D., suggests that, following a chromosome break, sister chromatids replicate and fuse, creating a chromosome with two centromeres joined by a DNA palindrome. What is known, however, is that such rearrangements are associated with the progression and prognosis of the cancer, Rattray said. How these events arise is not well understood. Some cancer cells exhibit massive genome rearrangements, which include gene amplifications, translocations, and deletions, and these rearrangements are often associated with the presence of a palindrome, suggesting a possible correlation between the palindrome and the gene rearrangements. “Small hairpins are not problematic, but when palindromes are long (more than 100 base pairs), they interfere with normal cellular processes such as transcription and replication,” she explained. For example, the sequence GGATCC on one strand of DNA is considered a palindrome because the sequence on its complementary strand is CCTAGG.īecause of the sequence complementarity, palindromic sequences can also fold back onto themselves, forming hairpin loops or cruciforms that are extruded from the normal double helix, Rattray said.
What Is a DNA Palindrome?Ī palindromic sequence of nucleotides (which are labeled A, T, C, or G) occurs when complementary strands of DNA read the same in both directions, either from the 5-prime end or the 3-prime end. Rattray is a major contributor to research reported in BMC Genomics that describes the group’s newly developed method for genome-wide sequencing of DNA palindromes in a cancer cell line. The arrangement turned out to be a DNA palindrome, “opening the door to studying these elusive DNA motifs,” she said.Ī staff scientist in GRCBL, NCI Center for Cancer Research, Rattray said that, while their discovery occurred a number of years ago, their group continues to study DNA repair and rearrangements that result in abnormal repair “because of the association with certain cancers.” The group’s goal is to better understand the origin of these rearrangements, she added.
The DNA exhibited a “very specific, but weird, rearrangement,” she explained.
When Alison Rattray and colleagues in the Gene Regulation and Chromosome Biology Laboratory (GRCBL) examined a mutant yeast cell they had isolated in a screen, they noticed something strange. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications. Editor's note: Platinum Highlight articles are noteworthy publications selected periodically by Dr.
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