Preprint Review Version 1 This version is not peer-reviewed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.

Journal reference: J. Clin. Med. 2020, 9, 613
DOI: 10.3390/jcm9030613

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.

Subject Areas

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.

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.