Mammalian homologous recombination repair and cancer intervention

Zhiyuan Shen, Jac A. Nickoloff

Research output: Chapter in Book/Report/Conference proceedingChapter

12 Scopus citations


Homologous recombination (HR) is highly relevant to cancer intervention for two major reasons. First, defects or deregulation in HR systems are major contributing factors in tumorigenesis. HR is important for the accurate repair of DNA double-strand breaks and DNA interstrand crosslinks, and it restarts stalled or collapsed replication forks. During these processes, HR restores the gross structure of DNA with minimum probability of mutation. HR is also tightly co-ordinated with mitosis and cell cycle checkpoint regulation, to ensure that cells with excessive DNA damage have minimum chance of being propagated. Thus, HR plays pivotal roles in maintaining genome stability and preventing tumorigenesis. Although HR is generally an error-free DNA repair process, hyper-recombination, hypo-recombination and altered HR outcomes can all lead to genomic instability. Thus HR can be mutagenic and contribute to genomic instability when it is not properly regulated. Second, the status of HR in cancer cells may be used as a marker for tailoring individual cancer therapy and improving prognosis evaluation. Current studies are focused on the stepwise DNA structural changes that occur during HR, and on the identification and characterization of proteins involved in HR. There are two categories of HR proteins: those with enzymatic activity that directly promote the chemical reactions during HR, and accessory proteins that regulate HR enzymes and co-ordinate HR reactions with other important cellular processes. It is important to fully identify and characterize the proteins of both categories as they may serve as targets for cancer therapy, or as markers for diagnosis, prognosis and treatment monitoring. In addition, a detailed picture of HR protein structure and function may provide new opportunities for cancer intervention through improvements in our understanding of cellular responses to therapeutic DNA damage.

Original languageEnglish (US)
Title of host publicationDNA Repair, Genetic Instability, and Cancer
PublisherWorld Scientific Publishing Co.
Number of pages38
ISBN (Electronic)9789812706782
ISBN (Print)9789812700148
StatePublished - Jan 1 2007

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)


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