Factors That Affect the Formation of Chromosomal Translocations in Cells

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2022 Oct 27

PMID 36291894

Authors

Reynand Jay Canoy

Anna Shmakova

Anna Karpukhina

Mikhail Shepelev

Diego Germini

Yegor Vassetzky

Affiliations

Soon will be listed here.

Abstract

Chromosomal translocations are products of the illegitimate repair of DNA double-strand breaks (DSBs). Their formation can bring about significant structural and molecular changes in the cell that can be physiologically and pathologically relevant. The induced changes may lead to serious and life-threatening diseases such as cancer. As a growing body of evidence suggests, the formation of chromosomal translocation is not only affected by the mere close spatial proximity of gene loci as potential translocation partners. Several factors may affect formation of chromosomal translocations, including chromatin motion to the potential sources of DSBs in the cell. While these can be apparently random events, certain chromosomal translocations appear to be cell-type-specific. In this review, we discuss how chromosomal translocations are formed and explore how different cellular factors contribute to their formation.

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References

Ginno P, Lott P, Christensen H, Korf I, Chedin F . R-loop formation is a distinctive characteristic of unmethylated human CpG island promoters. Mol Cell. 2012; 45(6):814-25. PMC: 3319272. DOI: 10.1016/j.molcel.2012.01.017. View

Lieber M . The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem. 2010; 79:181-211. PMC: 3079308. DOI: 10.1146/annurev.biochem.052308.093131. View

Falk M, Lukasova E, Kozubek S . Chromatin structure influences the sensitivity of DNA to gamma-radiation. Biochim Biophys Acta. 2008; 1783(12):2398-414. DOI: 10.1016/j.bbamcr.2008.07.010. View

Moynahan M, Jasin M . Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nat Rev Mol Cell Biol. 2010; 11(3):196-207. PMC: 3261768. DOI: 10.1038/nrm2851. View

Cremer T, Cremer M, Dietzel S, Muller S, Solovei I, Fakan S . Chromosome territories--a functional nuclear landscape. Curr Opin Cell Biol. 2006; 18(3):307-16. DOI: 10.1016/j.ceb.2006.04.007. View

Lemaitre C, Grabarz A, Tsouroula K, Andronov L, Furst A, Pankotai T . Nuclear position dictates DNA repair pathway choice. Genes Dev. 2014; 28(22):2450-63. PMC: 4233239. DOI: 10.1101/gad.248369.114. View

Schuler F, Hirt C, Dolken G . Chromosomal translocation t(14;18) in healthy individuals. Semin Cancer Biol. 2003; 13(3):203-9. DOI: 10.1016/s1044-579x(03)00016-6. View

Stark J, Pierce A, Oh J, Pastink A, Jasin M . Genetic steps of mammalian homologous repair with distinct mutagenic consequences. Mol Cell Biol. 2004; 24(21):9305-16. PMC: 522275. DOI: 10.1128/MCB.24.21.9305-9316.2004. View

Helmrich A, Ballarino M, Tora L . Collisions between replication and transcription complexes cause common fragile site instability at the longest human genes. Mol Cell. 2011; 44(6):966-77. DOI: 10.1016/j.molcel.2011.10.013. View

10.

Pfeiffer P, Goedecke W, Obe G . Mechanisms of DNA double-strand break repair and their potential to induce chromosomal aberrations. Mutagenesis. 2000; 15(4):289-302. DOI: 10.1093/mutage/15.4.289. View

11.

Lin C, Shukla A, Grady J, Fink J, Dray E, Duijf P . Translocation Breakpoints Preferentially Occur in Euchromatin and Acrocentric Chromosomes. Cancers (Basel). 2018; 10(1). PMC: 5789363. DOI: 10.3390/cancers10010013. View

12.

Bristow R, Hill R . Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat Rev Cancer. 2008; 8(3):180-92. DOI: 10.1038/nrc2344. View

13.

Crosetto N, Mitra A, Silva M, Bienko M, Dojer N, Wang Q . Nucleotide-resolution DNA double-strand break mapping by next-generation sequencing. Nat Methods. 2013; 10(4):361-5. PMC: 3651036. DOI: 10.1038/nmeth.2408. View

14.

Duquette M, Pham P, Goodman M, Maizels N . AID binds to transcription-induced structures in c-MYC that map to regions associated with translocation and hypermutation. Oncogene. 2005; 24(38):5791-8. DOI: 10.1038/sj.onc.1208746. View

15.

Brassesco M, Montaldi A, Gras D, Queiroz R, Martinez-Rossi N, Tone L . MLL leukemia-associated rearrangements in peripheral blood lymphocytes from healthy individuals. Genet Mol Biol. 2011; 32(2):234-41. PMC: 3036920. DOI: 10.1590/S1415-47572009000200005. View

16.

Fraccaro M, Maraschio P, Pasquali F, TIEPOLO L, Zuffardi O, Giarola A . Male infertility and 13-14 translocation. Lancet. 1973; 1(7801):488. DOI: 10.1016/s0140-6736(73)91916-8. View

17.

Fraser J, Williamson I, Bickmore W, Dostie J . An Overview of Genome Organization and How We Got There: from FISH to Hi-C. Microbiol Mol Biol Rev. 2015; 79(3):347-72. PMC: 4517094. DOI: 10.1128/MMBR.00006-15. View

18.

Nambiar M, Raghavan S . Chromosomal translocations among the healthy human population: implications in oncogenesis. Cell Mol Life Sci. 2012; 70(8):1381-92. PMC: 11113647. DOI: 10.1007/s00018-012-1135-x. View

19.

Morin S, Eccles J, Iturriaga A, Zimmerman R . Translocations, inversions and other chromosome rearrangements. Fertil Steril. 2016; 107(1):19-26. DOI: 10.1016/j.fertnstert.2016.10.013. View

20.

Iarovaia O, Rubtsov M, Ioudinkova E, Tsfasman T, Razin S, Vassetzky Y . Dynamics of double strand breaks and chromosomal translocations. Mol Cancer. 2014; 13:249. PMC: 4289179. DOI: 10.1186/1476-4598-13-249. View