Telomeres and chromosomal translocations: There’s a ligase at the end of the translocation

Duncan M. Baird, Eric A. Hendrickson

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Scopus citations

Abstract

Chromosomal translocations are now well understood to not only constitute signature molecular markers for certain human cancers but often also to be causative in the genesis of that tumor. Despite the obvious importance of such events, the molecular mechanism of chromosomal translocations in human cells remains poorly understood. Part of the explanation for this dearth of knowledge is due to the complexity of the reaction and the need to archaeologically work backwards from the final product (a translocation) to the original unrearranged chromosomes to infer mechanism. Although not definitive, these studies have indicated that the aberrant usage of endogenous DNA repair pathways likely lies at the heart of the problem. An equally obfuscating aspect of this field, however, has also originated from the unfortunate species-specific differences that appear to exist in the relevant model systems that have been utilized to investigate this process. Specifically, yeast and murine systems (which are often used by basic science investigators) rely on different DNA repair pathways to promote chromosomal translocations than human somatic cells. In this chapter, we will review some of the basic concepts of chromosomal translocations and the DNA repair systems thought to be responsible for their genesis with an emphasis on underscoring the differences between other species and human cells. In addition, we will focus on a specific subset of translocations that involve the very end of a chromosome (a telomere). A better understanding of the relationship between DNA repair pathways and chromosomal translocations is guaranteed to lead to improved therapeutic treatments for cancer.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Pages89-112
Number of pages24
DOIs
StatePublished - 2018

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1044
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Bibliographical note

Funding Information:
Acknowledgements Work in the Hendrickson laboratory was supported in part by grants from the NIH (GM088351) and the NCI (CA154461 and CA190492). Work in the Baird laboratory was supported by the Cancer Research UK (C17199/A18246). Both authors thank previous and current members of their respective laboratories for their contributions to this work. EAH thanks Dr. Anja-Katrin Bielinsky (University of Minnesota) for her comments on the manuscript.

Keywords

  • A-NHEJ
  • C-NHEJ
  • Chromosomal translocations
  • DNA DSB Repair
  • HDR
  • LIGIII
  • LIGIV

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