Publications | Zierhut Lab

A microscopy reporter for cGAMP reveals rare cGAS activation following DNA damage, and a lack of correlation with micronuclear cGAS enrichment

Lebrec, V., Afshar, N., Davies, L.R., Kujirai, T., Kanellou, A., Tidu, F., and Zierhut, C.

bioRxiv (2024)

In this study, we describe a new microscopy reporter for cGAMP. Applying this to DNA damage induced by ionising irradiation and chemotherapy drugs, we show that cGAS activation by genotoxic stress is a rare event, which does not correlate with cGAS enrichment on micronuclei.

Potential cGAS-STING pathway functions in DNA damage responses, DNA replication and DNA repair

Zierhut, C.

DNA Repair, 133 (2023)

p53 and Innate Immune Signaling in Development and Cancer: Insights from a Hematologic Model of Genome Instability

Zierhut, C.

Cancer Res, 83 (2023)

Comment on Dressel et al., 2023.

Vaccinia E5 is a major inhibitor of the DNA sensor cGAS

Yang, N., Wang, Y., Dai, P., Li, T., Zierhut, C., Tan, A., Zhang, T., Xiang, J.Z., Ordureau, A., Funabiki, H., Chen, Z., and Deng, L.

Nat Commun, 14 (2023)

In this study, we identify an inhibitor of cGAS encoded by Vaccinia virus.

Structural basis for the inhibition of cGAS by nucleosomes

Kujirai, T.*, Zierhut, C.*, Takizawa, Y., Kim, R., Negishi, L., Uruma, N., Hirai, S., Funabiki, H., and Kurumizaka, H.

*Equal contribution

Science, 370 (2020), 455-458

In this study, using cryo-EM and in vitro reconstitution, we present the mechanistic basis for the inhibition of cGAS by nucleosomes.

Anchor 2

Regulation and Consequences of Self-DNA recognition by cGAS.

Zierhut, C.**, and Funabiki, H

**Corresponding author

Trends Cell Biol, 30 (2020), 594-605

In this review, we discuss how cGAS can be activated by self-DNA, and what is known about the ensuing cellular consequences.

Anchor 1

The Cytoplasmic DNA Sensor cGAS Promotes Mitotic Cell Death

Zierhut, C.**, Yamaguchi, N., Paredes, M., Luo, J.D., Carroll, T., and Funabiki, H.**

**Corresponding authors

Cell, 178 (2019), 302-305

In this study, we show that the innate immune sensor of pathogenic DNA, cGAS, is suppressed on chromatin, but activated under aberrant conditions such as mitotic arrest, where it promotes apoptosis.

Nucleosome-Dependent Pathways That Control Mitotic Progression

Funabiki, H., Jenness, C. and Zierhut, C.

Cold Spring Harb Symp Quant Biol 82, (2017), 173-185

VCP/p97 extracts sterically trapped Ku70/80 rings from DNA in double strand break repair

van den Boom, J., Wolf, M., Weimann, L., Schulze, N., Li, F., Kaschani, F., Riemer, A., Zierhut, C., Kaiser, M., Iliakis, G., Funabiki, H., Meyer, H.

Mol Cell, 64 (2016), 189-198

Nucleosome functions in spindle assembly and nuclear envelope formation

Zierhut, C.**, and Funabiki, H.

**Corresponding author

BioEssays, 37 (2015), 1074-1085

In this review, we describe the roles that nucleosomes play in orchestrating cellular organisation during the cell cycle.

Nucleosomal regulation of chromatin composition and nuclear assembly revealed by histone depletion

Zierhut, C.**, Jenness, C., Kimura, H., and Funabiki, H.**

**Corresponding authors

Nat Struct Mol Biol, 21 (2014), 617-625

In this study, we showed for the first time the physiological consequences of the absence of nucleosomes. We found that nucleosomes are directly required for assembly of nuclear pore complexes and mitotic spindles.

Survivin reads phosphorylated histone H3 threonine 3 to activate the mitotic kinase Aurora B

Kelly, AE., Ghenoiu, C., Xue, JZ., Zierhut, C., Kimura, H., and Funabiki, H.

Science, 330 (2010), 235-239

In this study, we showed that the association of the mitotic master kinase Aurora B with a mitotic histone phosphorylation triggers its activation.

Break dosage, cell cycle stage and DNA replication influence DNA double strand break response

Zierhut, C., and Diffley, JFX.

EMBO J, 27 (2008), 1875-1885

In this study we describe a method to quantify processing of DSBs. This assay revealed new aspects of eukaryotic break processing, such as cell-cycle regulation and previously unrecognised similarities to prokaryotic break processing. Detailed protocol can be found in Resources.

Mnd1 is required for meiotic interhomolog repair

Zierhut, C., Berlinger, M., Rupp, C., Shinohara, A. and Klein, F.

Curr Biol, 14 (2004), 752–762

This paper contains the functional description of a new DNA repair gene required for meiosis.