Telomere Dysfunction Triggers Palindrome Formation Independently of Double-Strand Break Repair Mechanisms

Abstract

Inverted chromosome duplications or palindromes are linked with genetic disorders and malignant transformation. They are considered by-products of DNA double-strand break (DSB) repair: the homologous recombination (HR) and the nonhomologous end joining (NHEJ). Palindromes near chromosome ends are often triggered by telomere losses. An important question is to what extent their formation depends upon DSB repair mechanisms. Here we addressed this question using yeast genetics and comparative genomic hybridization. We induced palindrome formation by passaging cells lacking any form of telomere maintenance (telomerase and telomere recombination). Surprisingly, we found that DNA ligase 4, essential for NHEJ, did not make a significant contribution to palindrome formation induced by telomere losses. Moreover RAD51, important for certain HR-derived mechanisms, had little effect. Furthermore RAD52, which is essential for HR in yeast, appeared to decrease the number of palindromes in cells proliferating without telomeres. This study also uncovered an important role for Rev3 and Rev7 (but not for Pol32) subunits of polymerase ζ in the survival of cells undergoing telomere losses and forming palindromes. We propose a model called short-inverted repeat-induced synthesis in which DNA synthesis, rather than DSB repair, drives the inverted duplication triggered by telomere dysfunction.

Persistent broken chromosome inheritance drives genome instability

“…Evidence for fold-back inversions has been found in the genomes of viruses (28), prokaryotes (29), is associated with genetic disease (22,30,31) and a variety of cancers (32-34) Moreover, fold-back inversions observed in human cancer cells having escaped telomere-driven crisis occur independently of DSB repair (35,36), consistent with our findings. Thus, we anticipate that this study will contribute to the understanding of rapid genome evolution, pathogenesis and tumorigenesis.…”

Palindromic Vectors, Symmetropy and Symmentropy as Symmetry Descriptors of Binary Data

“…The palindromic analysis of discrete sequences has partly revolutionized molecular biology and is widely used as shown by the following work [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ], to name a few. Very recently, the study of quantum behavior [ 9 ], encountered in palindromes within the DNA structure, revealed that the symmetry properties of the unitary structure, other than those present in classical palindromes, play an important role in the origin and cause of mutations.…”

Unitary Structure of Palindromes in DNA

“…Moreover, previous studies have shown that these palindromic oligonucleotides have remarkable immunogenetic properties and potantiate the induction of interferon release from natural killer cells [7,8]. However, above all the explanations regarding the functionality of palindrome, the best approach may be the ability of these specific sequences to form hairpin [9]. Nag and Kurst revealed that palindromic sequences present breakpoints during the cellular process which requires double-strand breaks such as meiosis [10].…”