The role of the core non-homologous end joining factors in carcinogenesis and cancer

Brock J. Sishc, Anthony J. Davis

Research output: Contribution to journalReview article

15 Citations (Scopus)

Abstract

DNA double-strand breaks (DSBs) are deleterious DNA lesions that if left unrepaired or are misrepaired, potentially result in chromosomal aberrations, known drivers of carcinogenesis. Pathways that direct the repair of DSBs are traditionally believed to be guardians of the genome as they protect cells from genomic instability. The prominent DSB repair pathway in human cells is the non-homologous end joining (NHEJ) pathway, which mediates template-independent re-ligation of the broken DNA molecule and is active in all phases of the cell cycle. Its role as a guardian of the genome is supported by the fact that defects in NHEJ lead to increased sensitivity to agents that induce DSBs and an increased frequency of chromosomal aberrations. Conversely, evidence from tumors and tumor cell lines has emerged that NHEJ also promotes chromosomal aberrations and genomic instability, particularly in cells that have a defect in one of the other DSB repair pathways. Collectively, the data present a conundrum: how can a single pathway both suppress and promote carcinogenesis? In this review, we will examine NHEJ’s role as both a guardian and a disruptor of the genome and explain how underlying genetic context not only dictates whether NHEJ promotes or suppresses carcinogenesis, but also how it alters the response of tumors to conventional therapeutics.

Original languageEnglish (US)
Article number81
JournalCancers
Volume9
Issue number7
DOIs
StatePublished - Jul 6 2017

Fingerprint

Chromosome Aberrations
Carcinogenesis
Genomic Instability
Genome
Neoplasms
Chromosomal Instability
Double-Stranded DNA Breaks
DNA
Tumor Cell Line
Ligation
Cell Cycle
Therapeutics

Keywords

  • Cancer
  • Cancer therapy
  • Carcinogenesis
  • DSB repair
  • Genomic instability
  • NHEJ

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

The role of the core non-homologous end joining factors in carcinogenesis and cancer. / Sishc, Brock J.; Davis, Anthony J.

In: Cancers, Vol. 9, No. 7, 81, 06.07.2017.

Research output: Contribution to journalReview article

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