Targeting DNA damage response pathways in cancer

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 23(2), P. 78 - 94

Published: Dec. 5, 2022

Language: Английский

---

The molecular basis and disease relevance of non-homologous DNA end joining

Nature Reviews Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 21(12), P. 765 - 781

Published: Oct. 19, 2020

Language: Английский

---

Loop extrusion as a mechanism for formation of DNA damage repair foci

Nature, Journal Year: 2021, Volume and Issue: 590(7847), P. 660 - 665

Published: Feb. 17, 2021

Language: Английский

---

53BP1: a DSB escort

Genes & Development, Journal Year: 2020, Volume and Issue: 34(1-2), P. 7 - 23

Published: Jan. 1, 2020

53BP1 is an enigmatic DNA damage response factor that gained prominence because it determines the efficacy of PARP1 inhibitory drugs (PARPi) in BRCA1-deficient cancers. Recent studies have elevated from its modest status (yet another) to master regulator double-strand break (DSB) repair pathway choice. Our review literature suggests alternative view. We propose has evolved avoid mutagenic outcomes and does so by controlling processing ends dynamics DSBs. The consequences deficiency, such as diminished PARPi cells altered damaged telomeres, can be explained this viewpoint. further some fidelity functions coevolved with class switch recombination (CSR) immune system. speculate that, rather than being deterministic DSB choice, a escort guards against illegitimate potentially tumorigenic recombination.

Language: Английский

---

DNA double-strand breaks induce H2Ax phosphorylation domains in a contact-dependent manner

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: June 22, 2020

Abstract Efficient repair of DNA double-strand breaks (DSBs) requires a coordinated Damage Response (DDR), which includes phosphorylation histone H2Ax, forming γH2Ax. This modification spreads beyond the DSB into neighboring chromatin, generating DDR platform that protects against end disassociation and degradation, minimizing chromosomal rearrangements. However, mechanisms determine breadth intensity γH2Ax domains remain unclear. Here, we show contacts site are primary determinants for landscapes. DSBs disrupt topological border permit extension both adjacent compartments. In contrast, near produce highly asymmetric platforms, with nearly absent from one broken end. Collectively, our findings lend insights basic mechanism how precise location may influence genome integrity.

Language: Английский

---

Chromatin arranges in chains of mesoscale domains with nanoscale functional topography independent of cohesin

Science Advances, Journal Year: 2020, Volume and Issue: 6(39)

Published: Sept. 24, 2020

Advanced FIB-SEM and 3D-SIM imaging uncover cohesin-independent chromatin arrangement into structural functional modules.

Language: Английский

---

4D Genome Rewiring during Oncogene-Induced and Replicative Senescence

Molecular Cell, Journal Year: 2020, Volume and Issue: 78(3), P. 522 - 538.e9

Published: March 26, 2020

To understand the role of extensive senescence-associated 3D genome reorganization, we generated genome-wide chromatin interaction maps, epigenome, replication-timing, whole-genome bisulfite sequencing, and gene expression profiles from cells entering replicative senescence (RS) or upon oncogene-induced (OIS). We identify heterochromatin domains (SAHDs). Differential intra- versus inter-SAHD interactions lead to formation foci (SAHFs) in OIS but not RS. This OIS-specific configuration brings active genes located genomic regions adjacent SAHDs close spatial proximity favors their expression. also DNMT1 as a factor that induces SAHFs by promoting HMGA2 Upon depletion, transition conformation akin senescence. These data show how multi-omics imaging can critical features RS discover determinants acute SAHF formation.

Language: Английский

---

The role of chromatin loop extrusion in antibody diversification

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 22(9), P. 550 - 566

Published: Feb. 15, 2022

Language: Английский

---

Super-resolution microscopy: a brief history and new avenues

Philosophical Transactions of the Royal Society A Mathematical Physical and Engineering Sciences, Journal Year: 2022, Volume and Issue: 380(2220)

Published: Feb. 14, 2022

Super-resolution microscopy (SRM) is a fast-developing field that encompasses fluorescence imaging techniques with the capability to resolve objects below classical diffraction limit of optical resolution. Acknowledged Nobel prize in 2014, numerous SRM methods have meanwhile evolved and are being widely applied biomedical research, all specific strengths shortcomings. While some capable nanometre-scale molecular resolution, others geared towards volumetric three-dimensional multi-colour or fast live-cell imaging. In this editorial review, we pick on latest trends field. We start brief historical overview both conceptual commercial developments. Next, highlight important parameters for successfully particular super-resolution modality. Finally, discuss importance reproducibility quality control significance open-source tools microscopy. This article part Theo Murphy meeting issue 'Super-resolution structured illumination (part 2)'.

Language: Английский

---

Structural variations in cancer and the 3D genome

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(9), P. 533 - 546

Published: June 28, 2022

Language: Английский

---