André Nussenzweig

A CDK1 phospho-switch reprograms TRAIP to unload replisomes in mitosis

The paper identifies a phospho-switch mechanism that reprograms TRAIP to ubiquitylate replisomes in mitosis, enabling disassembly of unreplicated DNA.

Recurrent patterns of TOP1-mediated neuronal genomic damage shared by major neurodegenerative disorders

The paper identifies a shared TOP1-mediated mutagenic mechanism in ALS, FTD, and AD through single-cell genomic analysis and experimental validation.

Mapping the genetic landscape of the DNA damage response with Cas12a-based combinatorial knockout screens

This study uses Cas12a-based knockout screens to identify genetic interactions in the DNA damage response, revealing synthetic lethal and buffering interactions with therapeutic implications.

Mutational and functional heterogeneity of homology-directed repair deficiency and clinical implications

The paper shows HRd is a continuum with functional and mutational heterogeneity, highlighting the need for refined molecular classification for precision interventions.

Conserved and Unique Features of Terminal Telomeric Sequences in ALT-Positive Cancer Cells

The paper uses END-seq to analyze telomere sequences in ALT-positive cancer cells, revealing conserved and unique features of terminal telomeric sequences.

Senataxin and DNA-PKcs Redundantly Promote Non-Homologous End Joining Repair of DNA Double Strand Breaks During V(D)J Recombination

The paper shows senataxin and DNA-PKcs redundantly support NHEJ repair of RAG-induced DSBs during V(D)J recombination, with senataxin's function overlapping with RECQL5 and HLTF.

Somatic instability of the FGF14-SCA27B GAA·TTC repeat reveals a marked expansion bias in the cerebellum

This study examines somatic instability of the FGF14 GAA·TTC repeat in SCA27B, finding a cerebellar-specific expansion bias and increased instability in cerebellar regions compared to other brain areas.

Transcription elongation factor ELOF1 is required for efficient somatic hypermutation and class switch recombination

This study identifies ELOF1 as a critical factor for somatic hypermutation and class switch recombination by facilitating RNAPII pausing and AID targeting.

A common flanking variant is associated with enhanced meiotic stability of the FGF14-SCA27B locus

The paper identifies a common flanking variant linked to increased meiotic stability at the FGF14-SCA27B repeat locus.

EXO1-mediated DNA repair by single-strand annealing is essential for BRCA1-deficient cells

This study shows that EXO1 is essential for survival of BRCA1-deficient cells and identifies it as a potential therapeutic target.

ARP2/3- and resection-coupled genome reorganization facilitates translocations

The paper shows that ARP2/3-dependent nuclear actin polymerization and DNA end-resection coordinate genome reorganization to facilitate homology-directed repair and prevent translocations.

DNA-PK Promotes DNA End Resection at DNA Double Strand Breaks in G0 cells

The paper shows DNA-PK promotes DNA end resection in G0 cells but not in G1 or G2 phase cells, revealing a cell cycle-specific role in DSB repair.

RIF1 acts in DNA repair through phosphopeptide recognition of 53BP1

This study identifies RIF1 as a phosphopeptide-binding protein that interacts with phosphorylated 53BP1 epitopes to facilitate DNA repair and modulate shieldin recruitment.

The Dystonia Gene THAP1 Controls DNA Double Strand Break Repair Choice

This study identifies a transcriptional network involving THAP1 that regulates SHLD1 expression, affecting DNA repair choice and linking DNA damage to dystonia.

Neuronal Enhancers are Hotspots For DNA Single-Strand Break Repair

The paper identifies DNA single-strand breaks (SSBs) accumulating at neuronal enhancers and shows their repair involves PARP1, XRCC1, and DNA polymerase β.

Dual Histone Methyl Reader ZCWPW1 Facilitates Repair of Meiotic Double Strand Breaks

This study identifies ZCWPW1 as a dual histone methylation reader essential for meiotic DSB repair in vertebrates, showing its co-expression and co-evolution with PRDM9.

ATM and PRDM9 Regulate SPO11-bound Recombination Intermediates During Meiosis

This study directly detects meiotic DSBs and resection in vertebrates using END-seq on mouse spermatocytes, identifying a novel recombination intermediate regulated by ATM and PRDM9.