On a break with the X: the role of repair of double-stranded DNA breaks in X-linked disease

Laura De Caris, Lucia Cecceroni, Hemanth Tummala

Research output: Contribution to journalArticle

Abstract

The problem of managing free reactive DNA ends in eukaryotic cells has resulted in the development of a number of mechanisms in order to ensure that free ends are rendered non-reactive, or that the double-strand DNA breaks generating the free ends are promptly repaired; or that if the cell requires the introduction of double-strand breaks in its DNA at some point in its life cycle, the generated free DNA ends would be subject to strictest management. Different mechanisms for dealing with double-strand breaks in DNA exist, contributing to the maintenance of the exquisite balance between entering an evolutionary dead end resulting from extremely faithful DNA repair and genome instability resulting from relaxed control of repair. Recombination-based mechanisms related to the mechanism for repair of double-strand breaks and template slippage during replication are believed to be able to account for multiplication of parts of the genome, generating regions of homology which may serve as sites for mispairing during meiotic and mitotic recombination, and resulting, in turn, in translocations, deletions and inversions. This is especially true for the X chromosome, which engages in homologous recombination with the partnering X chromosome in female meiosis, but will participate in only limited partial genomic exchange with the Y chromosome in male meiosis, providing ample opportunities for mispairing and non-allelic recombination. Several X-linked monogeneous diseases and even some chromosome diseases such as variants of Turner syndrome have been found to be related to non-allelic homologous recombination during male meiosis, resulting in various rearrangements of the X chromosome. Apparently, the mechanisms which protect the mammalian genomes from stagnation or, alternatively, from hypermutability, may not always perform adequately. The genome rearrangement disorders may be unfortunate manifestations of the ongoing process of reorganization of genetic architecture in the eukaryotic genomes, which is inherent to evolution.
Original languageEnglish
Pages (from-to)2829 - 2837
Number of pages9
JournalBiotechnology & Biotechnological Equipment
Volume26
Issue number2
DOIs
StatePublished - Apr 2012

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Double-Stranded DNA Breaks
Genome
Meiosis
X Chromosome
Genetic Recombination
DNA
Homologous Recombination
Genetic Processes
Turner Syndrome
Genomic Instability
Y Chromosome
Eukaryotic Cells
Life Cycle Stages
DNA Repair
Chromosomes

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De Caris, Laura; Cecceroni, Lucia; Tummala, Hemanth / On a break with the X : the role of repair of double-stranded DNA breaks in X-linked disease.

In: Biotechnology & Biotechnological Equipment, Vol. 26, No. 2, 04.2012, p. 2829 - 2837.

Research output: Contribution to journalArticle

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On a break with the X : the role of repair of double-stranded DNA breaks in X-linked disease. / De Caris, Laura; Cecceroni, Lucia; Tummala, Hemanth.

In: Biotechnology & Biotechnological Equipment, Vol. 26, No. 2, 04.2012, p. 2829 - 2837.

Research output: Contribution to journalArticle

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