Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Studies on the Pathogenesis of Chromosome Rearrangement

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 20591

Share This Special Issue

Special Issue Editors

Prof. Dr. Angela Bentivegna

E-Mail Website
Guest Editor

School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
Interests: glioblastoma; cancer stem cells; urothelial carcinoma; developmental disability; human cytogenetics
Special Issues, Collections and Topics in MDPI journals

Dr. Gaia Roversi

E-Mail Website
Guest Editor

School of Medicine and Surgery, University of Milano - Bicocca, Milan, Italy

Special Issue Information

Dear Colleagues,

Genome instability of meiotic chromosomes contributes enormously to mutational processes during human genome evolution, in association with human diseases and manifesting as polymorphic variation in populations. In addition, genome instability of mitotic chromosomes is the driving force that creates mutations and chromosome rearrangements, which finally lead to the development of cancers. Several major mechanisms have been proposed for human genome rearrangements, and these include nonallelic homologous recombination (NAHR), nonhomologous end-joining (NHEJ), and replication based mechanisms (RBMs), such as fork stalling and template switching (FoSTeS) and microhomology‐mediated break‐induced replication (MMBIR). Of these, NAHR results in recurrent rearrangements mediated by a common genomic structure or architecture in which the rearranged interval is flanked by paralogous repeat sequences or low-copy repeats (LCRs, also known as segmental duplications). Conversely, NHEJ and replication mechanisms are a major contributor to nonrecurrent genomic rearrangements wherein the rearrangement size, genomic extent, and breakpoint position at a genetic locus can differ amongst unrelated subjects. Moreover, complex exonic, genic, and chromosomal rearrangements can be generated in a single mutagenic event by chromothripsis‐like events. Chromothripsis, a chromosome catastrophe involving shattering and subsequent rearrangement of chromosomes in somatic cells, was first recognized in cancers. By contrast, chromoanasynthesis describes the analogous phenomenon in constitutional genomic disorders.

This Special Issue, “Studies on the Pathogenesis of Chromosome Rearrangement”, will cover a selection of recent research topics and current review articles in the field of chromosome rearrangement, both on a meiotic and mitotic level.

Prof. Dr. Angela Bentivegna
Dr. Gaia Roversi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Chromosome rearrangement
Human genome copy number variation (CNV)
DNA repair
DNA double-strand breaks (DSBs)
Micronuclei
NAHR
FoSTeS
MMBIR
Chromothripsis
Chromoanasynthesis

Published Papers (5 papers)

Download All Papers

Research

Jump to: Review

17 pages, 4375 KiB

Open AccessArticle

Human Chromosome 18 and Acrocentrics: A Dangerous Liaison

by Nicoletta Villa, Serena Redaelli, Elena Sala, Donatella Conconi, Lorenza Romitti, Emanuela Manfredini, Francesca Crosti, Gaia Roversi, Marialuisa Lavitrano, Ornella Rodeschini, Maria Paola Recalcati, Rocco Piazza, Leda Dalprà, Paola Riva and Angela Bentivegna

Int. J. Mol. Sci. 2021, 22(11), 5637; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115637 - 26 May 2021

Viewed by 3341

Abstract

The presence of thousands of repetitive sequences makes the centromere a fragile region subject to breakage. In this study we collected 31 cases of rearrangements of chromosome 18, of which 16 involved an acrocentric chromosome, during genetic screening done in three centers. We noticed a significant enrichment of reciprocal translocations between the centromere of chromosome 18 and the centromeric or pericentromeric regions of the acrocentrics. We describe five cases with translocation between chromosome 18 and an acrocentric chromosome, and one case involving the common telomere regions of chromosomes 18p and 22p. In addition, we bring evidence to support the hypothesis that chromosome 18 preferentially recombines with acrocentrics: (i) the presence on 18p11.21 of segmental duplications highly homologous to acrocentrics, that can justify a NAHR mechanism; (ii) the observation by 2D-FISH of the behavior of the centromeric regions of 18 respect to the centromeric regions of acrocentrics in the nuclei of normal subjects; (iii) the contact analysis among these regions on published Hi-C data from the human lymphoblastoid cell line (GM12878). Full article

(This article belongs to the Special Issue Studies on the Pathogenesis of Chromosome Rearrangement)

► Show Figures

Figure 1

13 pages, 1950 KiB

Open AccessArticle

RB Regulates DNA Double Strand Break Repair Pathway Choice by Mediating CtIP Dependent End Resection

by Yuning Jiang, Jason C. Yam, Clement C. Tham, Chi Pui Pang and Wai Kit Chu

Int. J. Mol. Sci. 2020, 21(23), 9176; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239176 - 01 Dec 2020

Cited by 12 | Viewed by 3038

Abstract

Inactivation of the retinoblastoma tumor suppressor gene (RB1) leads to genome instability, and can be detected in retinoblastoma and other cancers. One damaging effect is causing DNA double strand breaks (DSB), which, however, can be repaired by homologous recombination (HR), classical non-homologous end joining (C-NHEJ), and micro-homology mediated end joining (MMEJ). We aimed to study the mechanistic roles of RB in regulating multiple DSB repair pathways. Here we show that HR and C-NHEJ are decreased, but MMEJ is elevated in RB-depleted cells. After inducing DSB by camptothecin, RB co-localizes with CtIP, which regulates DSB end resection. RB depletion leads to less RPA and native BrdU foci, which implies less end resection. In RB-depleted cells, less CtIP foci, and a lack of phosphorylation on CtIP Thr847, are observed. According to the synthetic lethality principle, based on the altered DSB repair pathway choice, after inducing DSBs by camptothecin, RB depleted cells are more sensitive to co-treatment with camptothecin and MMEJ blocker poly-ADP ribose polymerase 1 (PARP1) inhibitor. We propose a model whereby RB can regulate DSB repair pathway choice by mediating the CtIP dependent DNA end resection. The use of PARP1 inhibitor could potentially improve treatment outcomes for RB-deficient cancers. Full article

(This article belongs to the Special Issue Studies on the Pathogenesis of Chromosome Rearrangement)

► Show Figures

Figure 1

Review

Jump to: Research

16 pages, 752 KiB

Open AccessReview

Insight into the Molecular Basis Underlying Chromothripsis

by Katarzyna Ostapińska, Borys Styka and Monika Lejman

Int. J. Mol. Sci. 2022, 23(6), 3318; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063318 - 19 Mar 2022

Cited by 8 | Viewed by 3397

Abstract

Chromoanagenesis constitutes a group of events that arise from single cellular events during early development. This particular class of complex rearrangements is a newfound occurrence that may lead to chaotic and complex genomic realignments. By that, chromoanagenesis is thought to be a crucial factor regarding macroevolution of the genome, and consequently is affecting the karyotype revolution together with genomic plasticity. One of chromoanagenesis-type of events is chromothripsis. It is characterised by the breakage of the chromosomal structure and its reassembling in random order and orientation which results in the establishment of derivative forms of chromosomes. Molecular mechanisms that underlie this phenomenon are mostly related to chromosomal sequestration throughout the micronuclei formation process. Chromothripsis is linked both to congenital and cancer diseases, moreover, it might be detected in subjects characterised by a normal phenotype. Chromothripsis, as well as the other chromoanagenetic variations, may be confined to one or more chromosomes, which makes up a non-uniform variety of karyotypes among chromothriptic patients. The detection of chromothripsis is enabled via tools like microarray-based comparative genomic hybridisation, next generation sequencing or authorial protocols aimed for the recognition of structural variations. Full article

(This article belongs to the Special Issue Studies on the Pathogenesis of Chromosome Rearrangement)

► Show Figures

Figure 1

37 pages, 8043 KiB

Open AccessReview

Congenital Diseases of DNA Replication: Clinical Phenotypes and Molecular Mechanisms

by Megan Schmit and Anja-Katrin Bielinsky

Int. J. Mol. Sci. 2021, 22(2), 911; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020911 - 18 Jan 2021

Cited by 20 | Viewed by 6764

Abstract

Deoxyribonucleic acid (DNA) replication can be divided into three major steps: initiation, elongation and termination. Each time a human cell divides, these steps must be reiteratively carried out. Disruption of DNA replication can lead to genomic instability, with the accumulation of point mutations or larger chromosomal anomalies such as rearrangements. While cancer is the most common class of disease associated with genomic instability, several congenital diseases with dysfunctional DNA replication give rise to similar DNA alterations. In this review, we discuss all congenital diseases that arise from pathogenic variants in essential replication genes across the spectrum of aberrant replisome assembly, origin activation and DNA synthesis. For each of these conditions, we describe their clinical phenotypes as well as molecular studies aimed at determining the functional mechanisms of disease, including the assessment of genomic stability. By comparing and contrasting these diseases, we hope to illuminate how the disruption of DNA replication at distinct steps affects human health in a surprisingly cell-type-specific manner. Full article

(This article belongs to the Special Issue Studies on the Pathogenesis of Chromosome Rearrangement)

► Show Figures

Figure 1

17 pages, 999 KiB

Open AccessReview

Origin, Regulation, and Fitness Effect of Chromosomal Rearrangements in the Yeast Saccharomyces cerevisiae

by Xing-Xing Tang, Xue-Ping Wen, Lei Qi, Yang Sui, Ying-Xuan Zhu and Dao-Qiong Zheng

Int. J. Mol. Sci. 2021, 22(2), 786; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020786 - 14 Jan 2021

Cited by 1 | Viewed by 3141

Abstract

Chromosomal rearrangements comprise unbalanced structural variations resulting in gain or loss of DNA copy numbers, as well as balanced events including translocation and inversion that are copy number neutral, both of which contribute to phenotypic evolution in organisms. The exquisite genetic assay and gene editing tools available for the model organism Saccharomyces cerevisiae facilitate deep exploration of the mechanisms underlying chromosomal rearrangements. We discuss here the pathways and influential factors of chromosomal rearrangements in S. cerevisiae. Several methods have been developed to generate on-demand chromosomal rearrangements and map the breakpoints of rearrangement events. Finally, we highlight the contributions of chromosomal rearrangements to drive phenotypic evolution in various S. cerevisiae strains. Given the evolutionary conservation of DNA replication and recombination in organisms, the knowledge gathered in the small genome of yeast can be extended to the genomes of higher eukaryotes. Full article

(This article belongs to the Special Issue Studies on the Pathogenesis of Chromosome Rearrangement)

► Show Figures