Vincenzo Costanzo

The Expanding Roles of Homologous Recombination Proteins in Genome Stability
@labvincenzo.bsky.social review how RAD51 shields DNA from nucleolytic processing, promotes fork reversal, suppresses replicative DNA gaps, binds abasic sites to avert cytotoxic conversion
link.springer.com/article/10.1...

Happy to share new work from my lab by co-authors Peng and Lee-when BRCA1 is absent, RAD51 is busy authors.elsevier.com/sd/article/S...

Come and join us to celebrate the 10th anniversary of the BCGB, with a great selection of international speakers! Very convenient conference, open to anyone interested in the field of genome biology!

Three days, fresh data, & sparkly debates on how replication gaps drive cancer & disease. Grateful for every talk & discussion. Thank you for pushing science forward—next stop: great papers. Science moves fast when we move together! @albertociccia.bsky.social @labvincenzo.bsky.social

Three days, fresh data, & sparkly debates on how replication gaps drive cancer & disease. Grateful for every talk & discussion. Thank you for pushing science forward—next stop: great papers. Science moves fast when we move together!

Happy to share our DNA Repair special issue on the replication stress response curated with @vindignilab.bsky.social.
www.sciencedirect.com/special-issu...

Scientific Officer - Target Validation and DNA Damage Response Group (Prof Andrew Tutt) in Chelsea | The Institute of Cancer Research View details and apply for this Scientific Officer - Target Validation and DNA Damage Response Group (Prof Andrew Tutt) vacancy in Chelsea . Salary : Commencement on the salary range is s...

Interested in starting your cancer research career in London ?We're looking for a Scientific Officer to support our work on synthetic lethality in triple negative and BRCA1/2 mutant cancers. Ideal job for a new graduate who wants to kick start their research career. jobs.icr.ac.uk/vacancies/12...

📢 For all DNA fiber enthusiasts! 🟥🟩 We are thrilled to announce the release of our long-awaited AI-based workflow for the automated and quantitative analysis of DNA fibers. It's an exciting step forward—check it out on bioRxiv! lnkd.in/dQWUPtsP

🙏 Thank you, @3reak.bsky.social, @labvincenzo.bsky.social, and Evident, for fantastic collaboration! Special thanks go to the exceptionally talented postdoc Paolo Fagherazzi and the brilliant image analysis specialist Timo Diekmann for their extraordinary efforts! 🙏

www.science.org/doi/10.1126/...

Structural mechanism of strand exchange by the RAD51 filament. Homologous Recombination (HR) preserves genomic stability by repairing double-strand DNA breaks and ensuring efficient DNA replication. Central to HR is the strand-exchange reaction taking place within the three-stranded synapsis wherein a RAD51 nucleoprotein filament binds to a donor DNA. Here we present the cryoEM structure of a displacement loop of human RAD51 that captures the synaptic state when the filament has become tightly bound to the donor DNA. The structure elucidates the mechanism of strand exchange by RAD51, including the filament engagement with the donor DNA, the strand invasion and pairing with the complementary sequence of the donor DNA, the capture of the non-complementary strand and the polarity of the strand-exchange reaction. Our findings provide fundamental mechanistic insights into the biochemical reaction of eukaryotic HR. ### Competing Interest Statement The authors have declared no competing interest.

Over five years of work has gone into our new preprint! The #cryoEM structure of a human RAD51 filament caught at the point of strand exchange 🧬
www.biorxiv.org/content/10.1...

YouTube video by KeystoneSymposia KSQA: Dr. Kyungjae Myung (DNA Replication Gaps)

Submit poster abstracts by 4/3, 11:59pm MST for DNA Replication Gaps, Cancer, and Disease in Daejeon, South Korea. Join experts to explore DNA errors and cancer. keysym.us/KSDNARep25.

youtu.be/_aPIkDQg1rw #KSDNARep25 @cantorlab.bsky.social @albertociccia.bsky.social @labvincenzo.bsky.social

PAF15-PCNA assembly exhaustion governs lagging strand replication and replisome integrity Genome replication in eukaryotic cells is surveyed by the S-phase checkpoint, which orchestrates sequential replication origin activation to avoid exhaustion of hitherto poorly defined rate-limiting r...

Thrilled to share our lab's first preprint, led by an exceptional PhD student Gita Chhetri and with the support of wonderful collaborators, we find that replisome function is rate-limited by strand-specific PCNA dynamics. Hope you will enjoy reading.

www.biorxiv.org/content/10.1...

Brief teaser:

The homologous recombination factors BRCA2 and PALB2 interplay with mismatch repair pathways to maintain centromere stability and cell viability Graham et al. demonstrate that BRCA2 and PALB2 protect centromere integrity in non-cancerous cells through distinct mechanisms, partly counteracting the mismatch repair factor MLH1. In cancer cells, B...

We are delighted to share our latest work, characterising the role of BRCA2 and its binding partner PALB2 at centromeres, just out in the latest issue of Cell Reports. ⬇️

www.cell.com/cell-reports...

📣 Register now for the next Genome Instability and Human Disease course at @institutcurie.bsky.social! Gain knowledge on genome stability, from fundamental molecular pathways up to large scale approaches.

▶️training.institut-curie.org/courses/genome-instability-and-human-disease-2025

Symposium speakers and title

NAR Cancer 5th anniversary symposium on manipulating DNA repair and the DDR - Session 2 this Thursday, Feb 13, noon US Eastern time. Kara Bernstein and Joanna Loizou speaking. In collaboration with Social DNAing. Information and free registration link at academic.oup.com/narcancer/pa...

Dear all,

Postdoc positions are available to work on (1) the role of DNA strand break repair proteins during DNA replication and (2) the molecular/structural biology of XRCC1 protein complexes, as part of our work on genetic diseases & cancer. Contact me if interested: k.w.caldecott@sussex.ac.uk

Join the first Keystone conference dedicated to DNA replication gaps and cancer! Send an abstract to be selected for a talk.

www.keystonesymposia.org/conferences/...

Targeting BRCA1-deficient PARP inhibitor-resistant cells with nickases reveals nick resection as a cancer vulnerability Nature Cancer - Whalen et al. report that increased DNA end resection in BRCA-deficient, PARP inhibitor-resistant cancers leads to increased sensitivity to DNA nicks, limiting tumor formation in...

Congratulations to Jenna Whalen on her Nature Cancer paper out today-a distinct take on nicks and their toxicity! rdcu.be/d60Td

Join the first Keystone conference dedicated to DNA replication gaps and cancer! Send an abstract to be selected for a talk.

www.keystonesymposia.org/conferences/...

Join Helle D. Ulrich & experts this April to explore DNA replication errors, breaks, repair, and cancer! Submit abstracts and scholarships by Jan. 28 (11:59pm MST)! keysym.us/KSDNARep25

#KSDNARep25 #DNAreplicationgaps @cantorlab.bsky.social @albertociccia.bsky.social @labvincenzo.bsky.social

I have received a Wellcome Discovery Award to study the initiation of eukaryotic DNA replication, with 8 years of funding at the Francis Crick Institute.

Looking for a postdoc in molecular mechanisms, cryo-EM, cryo-FIB and in situ structure? Contact me now!

3 postdoc positions advertised soon.

Molecular basis of FIGNL1 in dissociating RAD51 from DNA and chromatin Maintaining genome integrity is an essential and challenging process. RAD51 recombinase, the central player of several crucial processes in repairing DNA and protecting genome integrity, forms filamen...

www.science.org/doi/10.1126/...

Groundbreaking, first ever meeting dedicated to DNA GAPS
📅 Save the Date: April 27-30, 2025 | Daejeon, South Korea www.keystonesymposia.org/conferences/...

RAD51 protects abasic sites to prevent replication fork breakage Hanthi et al. found that RAD51 recognizes and binds to abasic sites. Together with BRCA2, RAD51 prevents the accumulation of abasic site-induced replicative DNA gaps (caused by DNA methylation, oxidat...

Nice to be here! Take a look at our recent paper. Hope you like it: www.cell.com/molecular-ce...