A5027891696- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- PARP inhibition in cancer therapy
- Genomics and Chromatin Dynamics
- Pluripotent Stem Cells Research
- Genetics and Neurodevelopmental Disorders
- Epigenetics and DNA Methylation
- DNA and Nucleic Acid Chemistry
National Human Genome Research Institute
2020-2022
National Cancer Institute
2021-2022
Cancer Institute (WIA)
2021-2022
National Institutes of Health
2021
Neurons harbor high levels of single-strand DNA breaks (SSBs) that are targeted to neuronal enhancers, but the source this endogenous damage remains unclear. Using two systems postmitotic lineage specification-induced pluripotent stem cell-derived neurons and transdifferentiated macrophages-we show thymidine glycosylase (TDG)-driven excision methylcytosines oxidized with ten-eleven translocation enzymes (TET) is a SSBs. Although macrophage differentiation favors short-patch base repair fill...
Totipotent cells have the ability to generate embryonic and extra-embryonic tissues. Interestingly, a rare population of with totipotent-like potential, known as 2 cell (2C)-like cells, has been identified within ESC cultures. They arise from display similar features those found in 2C embryo. However, molecular determinants 2C-like conversion not completely elucidated. Here, we show that CCCTC-binding factor (CTCF) is barrier for reprogramming. Indeed, forced state by transcription DUX...
Double-strand break (DSB) repair choice is greatly influenced by the initial processing of DNA ends. 53BP1 limits formation recombinogenic single-strand (ssDNA) in BRCA1-deficient cells, leading to defects homologous recombination (HR). However, exact mechanisms which inhibits DSB resection remain unclear. Previous studies have identified two potential pathways: protection against DNA2/EXO1 exonucleases presumably through Shieldin (SHLD) complex binding ssDNA, and localized synthesis...
DNA double-strand break (DSB) repair by homologous recombination is confined to the S and G
DNA double-strand break (DSB) repair by homologous recombination (HR) is thought to be restricted the S- and G2- phases of cell cycle in part due 53BP1 antagonizing end resection G1-phase non-cycling quiescent (G0) cells. Here, we show that LIN37, a component DREAM transcriptional repressor, functions 53BP1-independent manner prevent HR G0 Loss LIN37 leads expression proteins, including BRCA1, BRCA2, PALB2, RAD51, promotes cells even presence 53BP1. In contrast 53BP1-deficiency,...
SUMMARY Totipotent cells have the ability of generating embryonic and extra-embryonic tissues 1,2 . Interestingly, a rare population with totipotent-like potential was identified within ESC cultures 3 These cells, known as 2 cell (2C)-like arise from display similar features to those found in totipotent embryo 2-4 However, molecular determinants 2C-like conversion not been completely elucidated. Here, we show that CTCF is barrier for reprogramming. Indeed, forced state by DUX expression...
Abstract DNA double strand break (DSB) repair by homologous recombination (HR) is thought to be restricted the S- and G 2 - phases of cell cycle in part due 53BP1 antagonizing end resection 1 -phase non-cycling quiescent (G 0 ) cells. Here, we show that LIN37, a component DREAM transcriptional repressor, functions 53BP1-independent manner prevent HR Loss LIN37 leads expression proteins, including BRCA1, BRCA2, PALB2 RAD51, cells even presence 53BP1. In contrast 53BP1-deficiency,...
Abstract DNA double-strand break (DSB) repair by homologous recombination is confined to the S and G 2 phases of cell cycle partly due 53BP1 antagonizing end resection in 1 phase non-cycling quiescent (G 0 ) cells where DSBs are predominately repaired non-homologous joining (NHEJ). Unexpectedly, we uncovered extensive MRE11- CtIP-dependent at mammalian cells. A whole genome CRISPR/Cas9 screen revealed DNA-dependent kinase (DNA-PK) complex as a key factor promoting In agreement, depletion...