- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- CRISPR and Genetic Engineering
- Endoplasmic Reticulum Stress and Disease
- PARP inhibition in cancer therapy
- Mitochondrial Function and Pathology
The Netherlands Cancer Institute
2021-2022
Hospital Universitario de Canarias
2020
MAD2L2 (REV7) plays an important role in DNA double-strand break repair. As a member of the shieldin complex, consisting MAD2L2, SHLD1, SHLD2 and SHLD3, it controls repair pathway choice by counteracting end-resection. Here we investigated requirements for complex assembly activity. Besides dimerization-surface, HORMA-domain protein has extraordinary ability to wrap its C-terminus around likely creating very stable complex. We show that appropriate function within requires dimerization,...
Abstract Protection of stalled replication forks is essential to prevent genome instability, a major driving force tumorigenesis. Several key regulators DNA double-stranded break (DSB) repair, including 53BP1 and RIF1, have been implicated in fork protection. MAD2L2, also known as REV7, plays an important role downstream 53BP1/RIF1 by counteracting resection at DSBs the recently discovered shieldin complex. The ability bind counteract exposed ends makes MAD2L2/shieldin prime candidate for...
Claspin is a multifunctional protein that participates in physiological processes essential for cell homeostasis are often defective cancer, namely due to genetic changes. It conceivable gene (CLSPN) alterations may contribute cancer development. Therefore, CLSPN germline were characterized sporadic and familial breast glioma samples, as well six lines. Their association susceptibility functional impact investigated. Eight variants identified (c.-68C>T, c.17G>A, c.1574A>G,...