Fragile site instability: Measuring more than breaks

Irina Waisertreiger, Jacqueline Barlow

Research output: Contribution to journalArticlepeer-review

Abstract

Genome instability is not only a hallmark of cancer, it is necessary for its initiation and evolution, and naturally accumulates as cells age. Replication stress is a potent source of genome instability found in many tumor types [1]. Chromosomal fragile sites are genomic loci highly prone to DNA damage specifically from replication stress and are frequently mutated in cancer [2-4]. While tracking the origin of individual mutations has proved challenging, measuring DNA damage and repair at endogenous sites can offer key insights into understanding the etiology of cancer. In the past 15 years, the causal link between replication stress, oncogene activation, and tumor initiation and evolution has become increasingly clear [1, 5-9]. Replication-associated damage accumulates at early stages of tumorigenesis and may promote further transformation. Studying the causes and consequences of fragile site instability can offer a window into the earliest stages of carcinogenesis [10-13]. In particular, fragile site studies will help us understand the molecular underpinnings influencing the frequency of DNA breakage, successful repair processes suppressing genome instability, and unsuccessful repair leading to mutations and chromosome rearrangements. Of these, measuring successful repair is the most challenging as it leaves little evidence behind.

Original languageEnglish (US)
Pages (from-to)60-67
Number of pages8
JournalOncoscience
Volume7
Issue number9-10
DOIs
StatePublished - Sep 2020

Keywords

  • Common fragile site
  • DNA damage replication stress
  • Early replicating fragile site
  • Fluorescent hybridization in situ
  • Genome instability
  • Homologous recombination repair
  • Sister chromatid exchanges

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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