Work

POLQ suppresses interhomolog recombination and loss of heterozygosity at targeted DNA breaks

Year: 2020

Type: article

Abstract: Significance This manuscript identifies a pathway of recombination which joins DNA ends on two homologous chromosomes in human cells. This pathway supports efficient recombination at targeted DSBs and nicks, at frequencies exceeding those of the spontaneous recombination events that ameliorate genetic diseases in human blood and skin cells. Recombination is further stimulated by depletion of POLQ, a factor with both DNA polymerase and helicase activities. POLQ depletion causes an especially dramatic increase in the frequency of copy-neutral loss of heterozygosity (cnLOH) events. These results have immediate practical implications for therapeutic correction of both compound heterozygous and autosomal dominant mutations, and they identify a mechanistic origin for prominent but poorly understood mutagenic signatures in cancer.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.2008073117

Authors: Luther Davis, Kevin J. Khoo, Yinbo Zhang, Nancy Maizels

Institution: University of Washington

Language: English

Topic: DNA Repair Mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Cancer Institute