Lsd1 and lsd2 control programmed replication fork pauses and imprinting in fission yeast.

Cell Rep

Institut Pasteur, Dynamic of the Genome Unit, Department of Genomes and Genetic, UMR3525, Paris, France.

Published: December 2012

In the fission yeast Schizosaccharomyces pombe, a chromosomal imprinting event controls the asymmetric pattern of mating-type switching. The orientation of DNA replication at the mating-type locus is instrumental in this process. However, the factors leading to imprinting are not fully identified and the mechanism is poorly understood. Here, we show that the replication fork pause at the mat1 locus (MPS1), essential for imprint formation, depends on the lysine-specific demethylase Lsd1. We demonstrate that either Lsd1 or Lsd2 amine oxidase activity is required for these processes, working upstream of the imprinting factors Swi1 and Swi3 (homologs of mammalian Timeless and Tipin, respectively). We also show that the Lsd1/2 complex controls the replication fork terminators, within the rDNA repeats. These findings reveal a role for the Lsd1/2 demethylases in controlling polar replication fork progression, imprint formation, and subsequent asymmetric cell divisions.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909218PMC
http://dx.doi.org/10.1016/j.celrep.2012.10.011DOI Listing

Publication Analysis

Top Keywords

replication fork
16
lsd1 lsd2
8
fission yeast
8
imprint formation
8
replication
5
lsd2 control
4
control programmed
4
programmed replication
4
fork
4
fork pauses
4

Similar Publications

DNA replication stress underpins the vulnerability to oxidative phosphorylation inhibition in colorectal cancer.

Cell Death Dis

January 2025

Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.

Mitochondrial oxidative phosphorylation (OXPHOS) is a therapeutic vulnerability in glycolysis-deficient cancers. Here we show that inhibiting OXPHOS similarly suppresses the proliferation and tumorigenicity of glycolytically competent colorectal cancer (CRC) cells in vitro and in patient-derived CRC xenografts. While the increased glycolytic activity rapidly replenished the ATP pool, it did not restore the reduced production of aspartate upon OXPHOS inhibition.

View Article and Find Full Text PDF

Human DNA licensing initiates replication fork assembly and DNA replication. This reaction promotes the loading of the hMCM2-7 complex on DNA, which represents the core of the replicative helicase that unwinds DNA during S-phase. Here, we report the reconstitution of human DNA licensing using purified proteins.

View Article and Find Full Text PDF

To achieve replicative immortality, cancer cells must activate telomere maintenance mechanisms. In 10 to 15% of cancers, this is enabled by recombination-based alternative lengthening of telomeres pathways (ALT). ALT cells display several hallmarks including heterogeneous telomere length, extrachromosomal telomeric repeats, and ALT-associated PML bodies.

View Article and Find Full Text PDF

Mechanisms of tandem duplication in the cancer genome.

DNA Repair (Amst)

December 2024

Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Pathology, Harvard Medical School, Boston, MA 02115,  USA; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.

Tandem duplications (TD) are among the most frequent type of structural variant (SV) in the cancer genome. They are characterized by a single breakpoint junction that defines the boundaries and the size of the duplicated segment. Cancer-associated TDs often increase oncogene copy number or disrupt tumor suppressor gene function, and thus have important roles in tumor evolution.

View Article and Find Full Text PDF

Molecular dependencies and genomic consequences of a global DNA damage tolerance defect.

Genome Biol

December 2024

Division of Tumor Biology & Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.

Background: DNA damage tolerance (DDT) enables replication to continue in the presence of fork stalling lesions. In mammalian cells, DDT is regulated by two independent pathways, controlled by the polymerase REV1 and ubiquitinated PCNA, respectively.

Results: To determine the molecular and genomic impact of a global DDT defect, we studied Pcna;Rev1 compound mutants in mouse cells.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!