Unknown

Dataset Information

0

Werner Syndrome Helicase Is Required for the Survival of Cancer Cells with Microsatellite Instability.

ABSTRACT: Werner syndrome protein (WRN) is a RecQ enzyme involved in the maintenance of genome integrity. Germline loss-of-function mutations in WRN led to premature aging and predisposition to cancer. We evaluated synthetic lethal (SL) interactions between WRN and another human RecQ helicase, BLM, with DNA damage response genes in cancer cell lines. We found that WRN was SL with a DNA mismatch repair protein MutL homolog 1, loss of which is associated with high microsatellite instability (MSI-H). MSI-H cells exhibited increased double-stranded DNA breaks, altered cell cycles, and decreased viability in response to WRN knockdown, in contrast to microsatellite stable (MSS) lines, which tolerated depletion of WRN. Although WRN is the only human RecQ enzyme with a distinct exonuclease domain, only loss of helicase activity drives the MSI SL interaction. This SL interaction in MSI cancer cells positions WRN as a relevant therapeutic target in patients with MSI-H tumors.

SUBMITTER: Kategaya L 

PROVIDER: S-EPMC6441948 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Werner Syndrome Helicase Is Required for the Survival of Cancer Cells with Microsatellite Instability.

Kategaya Lorn L   Perumal Senthil K SK   Hager Jeffrey H JH   Belmont Lisa D LD  

iScience 20190318

Werner syndrome protein (WRN) is a RecQ enzyme involved in the maintenance of genome integrity. Germline loss-of-function mutations in WRN led to premature aging and predisposition to cancer. We evaluated synthetic lethal (SL) interactions between WRN and another human RecQ helicase, BLM, with DNA damage response genes in cancer cell lines. We found that WRN was SL with a DNA mismatch repair protein MutL homolog 1, loss of which is associated with high microsatellite instability (MSI-H). MSI-H c  ...[more]

Similar Datasets

Unknown Werner syndrome helicase is a selective vulnerability of microsatellite instability-high tumor cells.
| S-EPMC6435321 | biostudies-literature
Unknown Structure of the helicase core of Werner helicase, a key target in microsatellite instability cancers.
| S-EPMC7671478 | biostudies-literature
Genomics Werner Helicase Prevents Cell Death in Cancers with Microsatellite Instability
2020-10-01 | GSE149709 | GEO
Other Werner Helicase Prevents Cell Death in Cancers with Microsatellite Instability [PacBio]
2020-10-01 | GSE154124 | GEO
Other Werner Helicase Prevents Cell Death in Cancers with Microsatellite Instability (WGS)
2020-10-01 | GSE149708 | GEO
Proteomics Structure of the helicase core of Werner Helicase, a key target in microsatellite instability cancers
2020-11-11 | PXD018910 | Pride
Genomics Werner Helicase Prevents Cell Death in Cancers with Microsatellite Instability (ChIP-Seq)
2020-10-01 | GSE149707 | GEO
Other Werner Helicase Prevents Cell Death in Cancers with Microsatellite Instability (END-Seq)
2020-10-01 | GSE149706 | GEO
Genomics Werner Helicase Prevents Cell Death in Cancers with Microsatellite Instability
| PRJNA629771 | ENA
Unknown WRN helicase expression in Werner syndrome cell lines.
| S-EPMC102521 | biostudies-literature