Review
Version 1
Preserved in Portico This version is not peer-reviewed
Chromothripsis and DNA-repair Disorders
Version 1
: Received: 28 January 2020 / Approved: 29 January 2020 / Online: 29 January 2020 (11:58:58 CET)
A peer-reviewed article of this Preprint also exists.
Nazaryan-Petersen, L.; Bjerregaard, V.A.; Nielsen, F.C.; Tommerup, N.; Tümer, Z. Chromothripsis and DNA Repair Disorders. J. Clin. Med. 2020, 9, 613. Nazaryan-Petersen, L.; Bjerregaard, V.A.; Nielsen, F.C.; Tommerup, N.; Tümer, Z. Chromothripsis and DNA Repair Disorders. J. Clin. Med. 2020, 9, 613.
Abstract
Chromothripsis is a mutational mechanism leading to complex and relatively clustered chromosomal rearrangements resulting in diverse phenotypic outcomes depending on the involved genomic landscapes. It may occur both in the germ and the somatic cells resulting in congenital and developmental disorders and cancer, respectively. Asymptomatic individuals may be carriers of chromotriptic rearrangements and experience recurrent reproductive failures when two or more chromosomes are involved. Several mechanisms are postulated to underly chromothripsis. The most attractive hypothesis involves chromosome pulverization in micronuclei followed by incorrect reassembly of fragments through DNA repair to explain the clustered nature of the observed complex rearrangements. Moreover, exogenous or endogenous DNA damage induction and dicentric bridge formation may be involved. Chromosome instability is commonly observed in the cells of patients with DNA-repair disorders, such as ataxia telangiectasia, Nijmegen breakage syndrome and Bloom syndrome. In addition, germline variations of TP53 have been associated with chromothripsis in Sonic-Hedgehog medulloblastoma and acute myeloid leukemia. In the present review, we focus on the underlying mechanisms of chromothripsis and the involvement of defective DNA-repair genes resulting in chromosome instability and chromothripsis-like rearrangements.
Keywords
chromothripsis; structural variants; DNA-repair; DNA-repair disorders; DNA-double strand breaks (DSBs); ataxia telangiectasia mutated (ATM); ataxia-telangiectasia and Rad3-related (ATR); TP53; micronuclei; chromosome pulverization.
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Comments (0)
We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.
Leave a public commentSend a private comment to the author(s)
* All users must log in before leaving a comment