A big week for the lab! Two new papers on how cells repair DNA double-strand breaks: one on getting NHEJ started in chromatin, one on processing the ends before ligation. Years of work by a fantastic team.
ZhaoLab
@zhaolabski.bsky.social
We study chromosomal replication & recombinational repair mechanisms, Smc5/6, SUMO-based controls using multidisciplinary approaches. Tweets are a group effort.
Meet #MSKPostdoc Cory Haluska from the @zhaolabski.bsky.social. When DNA repair creates tangled 🧬genetic structures, Cory investigates how cells safely untangle them to preserve genome stability and prevent harmful chromosomal rearrangements. #NPAW2026
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
Now online! DDIAS shields single-stranded DNA in mitosis and promotes vertebrate brain development
4. A new @natcomms.nature.com paper from @zhaolabski.bsky.social that revealed how DNA and ATP binding by the subunits of Smc5/6 enable its efficient SUMOylation of genome maintenance proteins. ACS supported this via @fanj1.bsky.social's postdoctoral fellowship. 🔗 doi.org/10.1038/s414...
Multi-subunit collaboration enables Smc5/6 to function as a composite SUMO E3 complex - Nature Communications
SUMO ligases conjugate the SUMO modifier to target proteins, thus regulating their functions. Here, the authors reveal how DNA and ATP binding by the multiple subunits of the SUMO ligase complex Smc5/...
doi.org
A study by @zhaolabski.bsky.social at @mskeducation.bsky.social and colleagues reveal how DNA and ATP binding by the multiple subunits of the SUMO ligase complex Smc5/6 enable its efficient SUMOylation of genome maintenance proteins
Multi-subunit collaboration enables Smc5/6 to function as a composite SUMO E3 complex - Nature Communications
SUMO ligases conjugate the SUMO modifier to target proteins, thus regulating their functions. Here, the authors reveal how DNA and ATP binding by the multiple subunits of the SUMO ligase complex Smc5/6 enable its efficient SUMOylation of genome maintenance proteins.
dlvr.it
Delighted to announce #RecombMechanisms is back for its 3rd edition next July! This conference will bring together leaders in the fields of DNA recombination (mitotic & meiotic), repair, replication, transcription, epigenetics, and cancer biology. Sign up for updates now➡️https://bit.ly/4pFcLAq
Excited to finally share our preprint on mapping the genetic interaction network of the DNA damage response with combinatorial knockout screens led by Sam Hayward, Alina Vaitsiankova, and Tomas Lama-Diaz! www.biorxiv.org/cgi/content/...
Mapping the genetic landscape of the DNA damage response with Cas12a-based combinatorial knockout screens
The DNA damage response (DDR) is a complex network of cellular pathways that ensures the faithful maintenance of our genomes upon a wide array of genomic insults. To elucidate the functional architect...
biorxiv.org
How do you move from static DNA models to real-time mechanics? Join our next webinar to see how the team of Dr. Xiaolan Zhao at MSKCC uses the LUMICKS C-Trap to decode the molecular determinants of Smc5/6 association with DNA junctions. 🔗 web.lumicks.com/l/970813/202...
Explore SMC mechanism and regulation at EMBO Workshop "Threads of life: SMC complexes in #chromosome structure and dynamics" in #Bengaluru, IN, 13–18 Dec 2026. Registration/Abstract submission by 1 Apr/1 May https://meetings.embo.org/event/26-smc-complexes #EMBOThreadsOfLife #genesky #EMBOevents 🧪
Happy to share our perspective on the DNA translocation mechanism by the CMG helicase. DNA translocation by the CMG helicase: the helical inchworm model url: portlandpress.com/biochemsoctr...
DNA translocation by the CMG helicase: the helical inchworm model
Abstract. In all cells, hexameric helicases drive the unwinding of parental chromosomal DNA at replication forks to provide the single-stranded DNA templates required by replicative DNA polymerases. D...
portlandpress.com
Nice to see some yeast genetics in a Cell paper, where the authors test models based on single-molecule in vitro analysis. The combination of genetics and biochemistry often addresses questions most effectively. www.cell.com/cell/fulltex...
A non-catalytic role for RFC in PCNA-mediated processive DNA synthesis
The RFC clamp loader remains associated with PCNA beyond the loading step, supporting processive DNA replication by stabilizing the inherently unstable PCNA-polymerase ẟ complex.
cell.com
Join SGD at #Yeast26 for cutting-edge #yeast research, networking opportunities, engaging talks, poster sessions, and workshops, for everyone from early career scientists to experienced researchers! Abstract submission by Mar5, early registration ends Apr16. See you there! @genetics-gsa.bsky.social
Hi all! We developed CAD-C to map chromatin organization at high res in yeast. It revealed an unexpected tight alignment: nucleosomes covering the same sequence tend to be associated across sister chromatids. www.biorxiv.org/content/10.6... #3DGenome #chromatin #Cohesin #centromere
CAD-C reveals centromere pairing and near-perfect alignment of sister chromatids
Three-dimensional (3D) genome organization plays a central role in gene regulation, chromatin folding, and genome stability. Although chromosome-conformation capture (3C)-derived methods have revoluti...
biorxiv.org
Want to know how homologous recombination defects are caused upon loss of BRCA2? Check out our recent efforts in uncovering this phenomenon just out in Science! www.science.org/doi/10.1126/...
FIGNL1 inhibits homologous recombination in BRCA2 deficient cells by dissociating RAD51 filaments
Homologous recombination (HR) deficiency upon Breast Cancer Gene 2 (BRCA2) loss arises from defects in the formation of RAD51 nucleoprotein filaments. We demonstrate that loss of the anti-recombinase ...
science.org
Our paper in Science is out! @souravagrawal.bsky.social, @rlynn.bsky.social, @susvirkar.bsky.social, and the rest of the team show human RPA is a telomerase processivity factor essential for telomere maintenance. This reshapes our thinking about telomerase regulation. www.science.org/doi/10.1126/...
Human RPA is an essential telomerase processivity factor for maintaining telomeres
Telomerase counteracts telomere shortening by repeatedly adding DNA repeats to chromosome ends. We identified the replication protein A (RPA) heterotrimer as a telomerase processivity factor critical ...
science.org
Beautiful, layered argument for the use of model organisms, especially small ones, in research. A must read!
PREACH! www.nature.com/articles/s41...
Cryo-EM captures the elusive moment when E1 hands off SUMO to E2- a molecular relay that’s been mostly guesswork until now. The structures reveal E1 doing dramatic shape-shifting to line up perfectly for the transfer, like enzyme origami in action.
New online: Cryo-EM structures reveal the molecular mechanism of SUMO E1–E2 thioester transfer
Our paper is now out in Molecular Cell! Check the thread in this former post: www.cell.com/molecular-ce...
Chromatin architecture mapping by multiplex proximity tagging
Delamarre et al. develop a technology named PCP that can simultaneously map complex spatial relationships between millions of molecules. Using PCP, they investigate chromatin structure and describe si...
cell.com
Hi everyone! The latest method from the Whitehouse lab: PCP PCP uses a novel proximity barcoding strategy to simultaneously map 3D genome organization at various resolutions at the single molecule level: Out soon, check the updated BioRxiv – little thread: 1/11 www.biorxiv.org/content/10.1...
Interested in chromatin architecture? Checkout our new method - PCP - that can map genome organization as multi-way interactions as well as nucleosome footprint and nucleosome spacing at very high resolution. www.biorxiv.org/content/10.1...
Chromatin architecture mapping by multiplex proximity tagging
Chromatin plays a pivotal role in genome expression, maintenance, and replication. To better understand chromatin organization, we developed a novel proximity-tagging method which assigns unique DNA b...
biorxiv.org
How do replisomes walk on DNA? And what happens when they run into a G-quadruplex? @sahilbatra.bsky.social and @benallwein.bsky.social provide unexpected insight in our latest paper with Richard Hite @mskcancercenter.bsky.social @science.org www.science.org/doi/10.1126/.... Congrats to all authors!
G-quadruplex–stalled eukaryotic replisome structure reveals helical inchworm DNA translocation
DNA G-quadruplexes (G4s) are non–B-form DNA secondary structures that threaten genome stability by impeding DNA replication. To elucidate how G4s induce replication fork arrest, we characterized fork ...
science.org
Happy to share a new work from the lab on how DNA damage checkpoint can be down-regulated. rdcu.be/d5o3E. Congrats to all authors at @mskcancercenter.bsky.social and our Weill BCMB student @tzippora.bsky.social. gradschool.weill.cornell.edu/bcmb-allied-...
Our latest paper showing that DNA nicks drive expansions of both normal and disease-size alleles. All credit goes to a fantastic graduate student Liangzi Li as well as to a terrific team of current and former undergraduate and graduate students in the lab. www.pnas.org/doi/10.1073/pnas.2413298121
Recurrent DNA nicks drive massive expansions of (GAA)n repeats | PNAS
Over 50 hereditary degenerative disorders are caused by expansions of short tandem DNA repeats (STRs). (GAA)n repeat expansions are responsible for...
pnas.org
If you are interested in pursuing a PhD in biomedical sciences in New York City, it is still time to apply to the BCMB program run jointly by Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center ! Deadline: Dec 1, 2024.
Check out this list of ubiquitin and Ubl profiles to follow. Repost if you want me to add you to it. Let’s create a good community here ☁️ go.bsky.app/3VPQofn