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Bhak, Jong
KOrean GenomIcs Center(KOGIC)
Research Interests
  • Geromics, genomics, bioinformatics, protein Engineering, OMICS

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Defining the mutation signatures of DNA polymerase θ in cancer genomes

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Title
Defining the mutation signatures of DNA polymerase θ in cancer genomes
Author
Hwang, TaejooReh, ShelleyDunbayev, YerkinZhong, YiTakata, YokoShen, JianjunMcBride, Kevin MMurnane, John PBhak, JongLee, SeminWood, Richard DTakata, Kei-ichi
Issue Date
2020-09
Publisher
Oxford University Press
Citation
NAR Cancer, v.2, no.3
Abstract
DNA polymerase theta (POLQ)-mediated end joining (TMEJ) is a distinct pathway for mediating DNA double-strand break (DSB) repair. TMEJ is required for the viability of BRCA-mutated cancer cells. It is crucial to identify tumors that rely on POLQ activity for DSB repair, because such tumors are defective in other DSB repair pathways and have predicted sensitivity to POLQ inhibition and to cancer therapies that produce DSBs. We define here the POLQ-associated mutation signatures in human cancers, characterized by short insertions and deletions in a specific range of microhomologies. By analyzing 82 COSMIC (Catalogue of Somatic Mutations in Cancer) signatures, we found that BRCA-mutated cancers with a higher level of POLQ expression have a greatly enhanced representation of the small insertion and deletion signature 6, as well as single base substitution signature 3. Using human cancer cells with disruptions of POLQ, we further show that TMEJ dominates end joining of two separated DSBs (distal EJ). Templated insertions with microhomology are enriched in POLQ-dependent distal EJ. The use of this signature analysis will aid in identifying tumors relying on POLQ activity.
URI
https://scholarworks.unist.ac.kr/handle/201301/49298
URL
https://academic.oup.com/narcancer/article/2/3/zcaa017/5898153
DOI
10.1093/narcan/zcaa017
ISSN
2632-8674
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BME_Journal Papers
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