Review

International Journal of Oral Science (2011) 3, 176–179; doi:10.4248/IJOS11064

DNA repair and synthetic lethality

Gongshe Guo1, Fengmei Zhang1, Ruijie Gao2, Robert Delsite4, Zhihui Feng1,3 and Simon N Powell4

  1. 1School of Public Health, Shandong University, Jinan 250012, China
  2. 2Second People's Hospital of Weifang, Weifang 261041, China
  3. 3Department of Radiation Oncology, Washington University in St Louis, St Louis MO 63108, USA
  4. 4Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York NY 10065, USA

Correspondence: Zhihui Feng, Fax: 001 314 362 9790 E-mail: fengzhihui@sdu.edu.cn; Simon N Powell, Fax: 001 646 888 3200 E-mail: powells@mskcc.org

Received 18 June 2011; Accepted 10 July 2011

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Abstract

Tumors often have DNA repair defects, suggesting additional inhibition of other DNA repair pathways in tumors may lead to synthetic lethality. Accumulating data demonstrate that DNA repairdefective tumors, in particular homologous recombination (HR), are highly sensitive to DNAdamaging agents. Thus, HRdefective tumors exhibit potential vulnerability to the synthetic lethality approach, which may lead to new therapeutic strategies. It is well known that poly (adenosine diphosphate (ADP)ribose) polymerase (PARP) inhibitors show the synthetically lethal effect in tumors defective in BRCA1 or BRCA2 genes encoded proteins that are required for efficient HR. In this review, we summarize the strategies of targeting DNA repair pathways and other DNA metabolic functions to cause synthetic lethality in HRdefective tumor cells.

Keywords:

DNA repair; homologous recombination; synthetic lethality; BRCA; Rad52