#CIP2A
Fresh preprint from the lab: CIP2A tetramerization is required for mitotic DNA repair.

A fantastic collaboration with @marcelvanvugt.bsky.social. By @laurendehaan.bsky.social, @rebeccaschneeweiss.bsky.social, and colleagues from Groningen, Vienna, Leiden, and Amsterdam 🙌

doi.org/10.64898/202...
September 9, 2026 at 5:08 AM
Very pleased to share this new study: In a truly collaborative effort with the lab of Pim Huis in 't Veld @huis.bsky.social, we combined biochemistry with cell biological and genomic approaches to uncover how CIP2A works in mitotic DNA repair.

www.biorxiv.org/content/10.6...
CIP2A tetramerization is required for mitotic DNA repair
DNA lesions that persist in mitosis threaten genome stability. These lesions recruit TOPBP1-CIP2A, a complex crucial to tether and process damaged DNA on mitotic chromosomes. Importantly, CIP2A is syn...
www.biorxiv.org
August 24, 2026 at 3:28 PM
New work from the lab! 🔬

We report that DDIAS is a new component of the mitotic CIP2A-TOPBP1 pathway of genome maintenance. 1/n

www.biorxiv.org/content/10.1...
Mitotic single-stranded DNA suppression by DDIAS
Incomplete DNA replication and chromosome breakage during mitosis pose major threats to chromosome segregation. The CIP2A-TOPBP1 complex acts to mitigate this peril, but its exact role is not yet unde...
www.biorxiv.org
September 10, 2025 at 4:50 PM
Our latest work describing DDIAS as a new component of the TOPBP1-CIP2A pathway in mitosis and its requirement for brain development is now published. Fantastic collaboration with @fenaochs.bsky.social, @profstewartlab.bsky.social, Lars Allan Larsen, @tcr-miller.bsky.social, Zafar Iqbal & others
August 24, 2026 at 5:24 PM
Excited to share our lab’s latest preprint! We identify DDIAS as a novel single-stranded DNA-binding component of the TOPBP1–CIP2A complex, which acts in a mitotic DNA damage response pathway to protect chromosome integrity. Short summary below, and read it here: www.biorxiv.org/content/10.1...
DDIAS is a single-stranded DNA-binding effector of the TOPBP1-CIP2A complex in mitosis
DNA double-strand breaks and unresolved DNA replication intermediates are particularly dangerous during mitosis. Paradoxically, cells inactivate canonical DNA repair mechanisms during chromosome segre...
www.biorxiv.org
September 10, 2025 at 3:18 PM
New work from the lab! We report that DDIAS is a downstream effector of CIP2A-TOPBP1 in mitosis that suppresses ssDNA to preserve genome integrity. From the great @yiboxue.bsky.social and many collaborators!

Free link: authors.elsevier.com/a/1nfiF3vVUP...
Pay link: www.cell.com/molecular-ce...
August 24, 2026 at 11:37 PM
Extremely happy to share that my main PhD project about CIP2A-TOPBP1 and the SMX complex is now available online as pre-print.

Huge thanks to all co-authors but especially @marcelvanvugt.bsky.social for giving me the opportunity to work on this exciting project!

www.biorxiv.org/content/10.1...
CIP2A is required for mitotic recruitment of the SLX1/XPF/MUS81 tri-nuclease complex to replication stress-induced DNA lesions to maintain genome integrity
Perturbed DNA replication can lead to incompletely replicated DNA when cells enter mitosis and can interfere with chromosome segregation. Cells therefore require mechanisms to resolve these lesions du...
www.biorxiv.org
April 4, 2025 at 11:34 AM
Very nice bioinformatics analysis of the role of #CIP2A in ovarian cancer by @karteris.bsky.social
rdcu.be/exid3
Emerging roles of the cancerous inhibitor of protein phosphatase 2A (CIP2A) in ovarian cancer
Scientific Reports - Emerging roles of the cancerous inhibitor of protein phosphatase 2A (CIP2A) in ovarian cancer
rdcu.be
July 22, 2025 at 7:43 AM
🎉🎉 Thrilled that our project on CIP2A has been funded by the Swiss Cancer Research foundation @krebsliga.bsky.social for the next 3 years! Excited to deepen our studies and push the research forward. @ManuelStucki
January 31, 2025 at 2:20 PM
Have you heard of #CIP2A, a hot new kid on the block of genome integrity and DNA repair?
Funny enough, most of these papers hardly mention CIP2A as PP2A inhibitor covered by about 400 papers. This is really exciting developments for sure, an eventually these oncogenic arms of CIP2A will merge.
October 14, 2025 at 1:20 PM
#CIP2A has a druggable pocket. I am thrilled to announce that the last of my #CIP2A bucket list items, established 2007 has finally been accomplished. The work now out in BioRxiv reports a small molecule druggable pocket on CIP2A
1/2 www.biorxiv.org/content/10.1...
Modulation of CIP2A dimerization and protein stability via druggable pocket
Cancerous inhibitor of PP2A (CIP2A) supports malignant growth across several cancer types. CIP2A is also a synthetic lethal therapy target for BRCA-mutant cancers. In addition, CIP2A causes Alzheimer'...
www.biorxiv.org
October 15, 2025 at 5:57 AM
Delighted to share our lab's first preprint identifying DDIAS as a mitotic DNA repair protein. Great collaboration with the @andrewblackford.bsky.social, @tcr-miller.bsky.social and @profstewartlab.bsky.social labs, and many more. Read the paper here: www.biorxiv.org/content/10.1...
DDIAS is a single-stranded DNA-binding effector of the TOPBP1-CIP2A complex in mitosis
DNA double-strand breaks and unresolved DNA replication intermediates are particularly dangerous during mitosis. Paradoxically, cells inactivate canonical DNA repair mechanisms during chromosome segre...
www.biorxiv.org
September 10, 2025 at 7:01 PM
We'll be hosting Peter Martin (Niedzwiedz Lab, ICR London) tomorrow to discuss his recently baked preprint: "The mitotic CIP2A-TOPBP1 axis facilitates mitotic pathway choice between MiDAS and MMEJ" (buff.ly/4hYnS2u).

Thanks for accepting our invitation, we're looking forward to this JC!
The mitotic CIP2A-TOPBP1 axis facilitates mitotic pathway choice between MiDAS and MMEJ
Mitotic DNA double-strand breaks (DSBs) accumulate in response to replication stress or BRCA1/2 deficiency posing a significant threat to genome stability as repair by non-homologous end-joining…
buff.ly
March 3, 2025 at 8:07 AM
I am truly grateful for the opportunity to contribute to this exciting project revealing that CIP2A tetramerization via its C-terminus is required for DNA repair in mitosis.
August 24, 2026 at 4:30 PM
We uncovered synthetic lethal interactions between Fanconi anemia genes and GEN1, CIP2A, and RHNO1; the translesion polymerase REV1-Pol ζ and the MCM8/9-HROB DNA helicase; and the DNA translocase SMARCAL1 and the FANCM complex, as reported also by @durocher1.bsky.social and @jcornlab.bsky.social.
June 8, 2026 at 9:49 PM
CIP2A tetramerization is required for mitotic DNA repair https://www.biorxiv.org/content/10.64898/2026.08.22.746418v1
August 24, 2026 at 2:32 PM
Make sure to check out the exciting paper of @andrewblackford.bsky.social @fenaochs.bsky.social @profstewartlab.bsky.social et al. who also describe the identification of DDIAS, its role in the CIP2A pathway, and DDIAS/CIP2A mutations in neurodevelopmental disorders

www.cell.com/cell/fulltex...
DDIAS shields single-stranded DNA in mitosis and promotes vertebrate brain development
DDIAS is identified as a factor that protects single-stranded DNA during mitosis to maintain chromosome stability, and inactivating mutations in DDIAS are identified in a human neurodevelopmental diso...
www.cell.com
August 24, 2026 at 11:37 PM
DDIAS is a single-stranded DNA-binding effector of the TOPBP1-CIP2A complex in mitosis https://www.biorxiv.org/content/10.1101/2025.09.09.675193v1
September 10, 2025 at 1:17 PM
A PP2A-mtATR-tBid axis links DNA damage-induced CIP2A degradation to apoptotic dormancy and therapeutic resistance in PDAC 🧪 #PancreaticCancer www.sciencedirect.com/science/arti...
A PP2A-mtATR-tBid axis links DNA damage-induced CIP2A degradation to apoptotic dormancy and therapeutic resistance in PDAC
DNA damage-based drugs are widely used in cancer therapy, yet resistance remains a significant challenge. In this study, we uncovered a non-DNA repair…
www.sciencedirect.com
May 12, 2025 at 6:26 AM
New #PP2A research tools in @addgene.bsky.social by us. PME-1 lentivirus overexpression vectors for wild type and methylesterase and PP2Ac binding mutants www.addgene.org/browse/artic... Please check also our entire collection including various CIP2A tools. Enjoy www.addgene.org/Jukka_Wester...
Addgene: Westermarck PPME1 expression plasmids
www.addgene.org
April 1, 2025 at 6:34 PM
We purified full-length human CIP2A and found remarkably long structures: CIP2A rods that form via a short tetrameric antiparallel coiled coil. The tetramerization is crucial for POLQ-mediated signatures of mitotic DNA repair. Interfering with CIP2A tetramerization hypersensitizes HR-deficient cells
September 9, 2026 at 5:14 AM
More work is needed to unravel how CIP2A, a multimerizing spacer, exactly promotes a functional DNA damage response. One experiment to highlight: to test if CIP2A tetramerization is required and -to some degree- sufficient mitotic DNA repair, we swapped the C-terminal end of human CIP2A..
September 9, 2026 at 5:16 AM
Skiteam #CIP2A demonstrated admirable attitude and performance on yesterday´s training session. Some of the bravest with training background from the past years already approached the 3 km track with up and downhills. #lifeinfinland @westermarcklab.bsky.social #lifeoutsidethelab
January 18, 2026 at 9:29 AM
Kaima Tsukuda and @andrewblackford.bsky.social have a highly complementary study that indicates that mutations in DDIAS (and CIP2A) caused neurodevelopmental defects, pointing a role for this pathway in development. /fin

www.biorxiv.org/content/10.1...
DDIAS is a single-stranded DNA-binding effector of the TOPBP1-CIP2A complex in mitosis
DNA double-strand breaks and unresolved DNA replication intermediates are particularly dangerous during mitosis. Paradoxically, cells inactivate canonical DNA repair mechanisms during chromosome segre...
www.biorxiv.org
September 10, 2025 at 4:50 PM