![]() ![]() ![]() After denaturation of a short region of DNA at the center, intrastrand base pairing occurs and a small proto-cruciform forms which can further extrude into a larger cruciform. A cruciform structure forms in dsDNA by gradual extrusion which begins at the center of the palindrome. It is considered that a hairpin structure can occur in the single-stranded lagging strand during DNA replication. The loop either consists of bases within the spacer, if such region is present in a specific palindrome, or of four–six bases which lie in the center of symmetry of the two inverted repeats and cannot be complementarily paired due to the rigidity of the DNA strand. Each hairpin consists of a stem comprised of complementary paired inverted repeats and a loop. In the single-stranded DNA, a hairpin structure forms, while in the double-stranded DNA, a cruciform structure consisting of two hairpins, one in each strand, forms. If a palindrome is of sufficient length, intrastrand base pairing can occur and this results in formation of secondary structures in DNA ( Figure 1b). However, many of the discovered palindromes have no known biological function and can be relatively long (from several dozen to several hundred base pairs). Palindromes are found in genomes of all species investigated so far and they often play important roles as binding sites for homodimeric proteins, parts of promoters, replication origins or other regulatory sequences. The term quasipalindrome can be used to refer to a non-perfect palindrome. If the repeats (also called the palindrome arms) are identical and have no spacer in between, the palindrome is referred to as perfect. DNA Palidromes Can Form Secondary StructuresĪ palindrome in DNA is a sequence consisting of two identical or highly similar inverted repeats which are either adjacent to one another or separated by a spacer region ( Figure 1a). Finally, in Section 4, we overview the available data on palindrome number and distribution in eukaryotic genomes and discuss the newest experimental evidence regarding mechanisms underlying recurrent genetic rearrangements instigated by known palindromic sequences in the human genome.Ģ.1. We discuss the mechanisms of de novo palindrome formation and palindromic amplification in cancer cells, as well as possible roles preexisting DNA palindromes and short inverted repeats might have in these processes. Palindromic amplification of genes is one of the hallmarks of cancer cells and is often linked to poor treatment prognosis. In Section 3, we focus on the role DNA palindromes play in carcinogenesis. We explain why palindromes are recombinogenic and what is the current understanding of molecular mechanisms underlying palindrome recombinogenicity in eukaryotic cells. First, in Section 2 of this review, we explore the recombinogenic nature of palindromic sequences. As a response to the breakage (double-strand break-DSB) in DNA, the cell employs various repair mechanisms which can ultimately result in genetic rearrangements. The architecture of the genome is complex and wondrous, with sequences that play various important roles, but also those, such as DNA palindromes, that create fragile sites (i.e., sites prone to potentially lethal chromosome breakage), thus endangering genome stability. Furthermore, we overview the data on known palindromic sequences in the human genome and efforts to estimate their number and distribution, as well as underlying mechanisms of genetic rearrangements specific palindromic sequences cause.Īs the exploration of various genomes, including our own, moves forward thanks to ever more advanced and more easily available techniques, it is becoming clear that the genome is much more than the assembly of genes. ![]() Here, we bring an overview of current understanding and knowledge on molecular mechanisms of palindrome recombinogenicity and discuss possible implications of DNA palindromes in carcinogenesis. Given their recombinogenic nature, it is not surprising that palindromes in the human genome are involved in genetic rearrangements in cancer cells as well as other known recurrent translocations and deletions associated with certain syndromes in humans. The ability of certain palindromes to initiate genetic recombination lies in their ability to form secondary structures in DNA which can cause replication stalling and double-strand breaks. However, many palindromes are known as fragile sites in the genome, sites prone to chromosome breakage which can lead to various genetic rearrangements or even cell death. Certain palindromes have important biological functions as parts of various cis-acting elements and protein binding sites. A palindrome in DNA consists of two closely spaced or adjacent inverted repeats. ![]()
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