Related Experiment Video

Updated: Jan 27, 2026

Techniques to Induce and Quantify Cellular Senescence
06:51

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

35.0K

E2F1 mediates the downregulation of POLD1 in replicative senescence

Shichao Gao1, Qiao Song1, Jing Liu1

  • 1Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing, 100053, People's Republic of China.

Cellular and Molecular Life Sciences : CMLS
|March 22, 2019
PubMed

Insights

Age-related decline in transcription factor E2F1 and increased POLD1 promoter methylation reduce POLD1 expression, contributing to cellular aging. This study elucidates the molecular mechanisms behind POLD1 downregulation in aging cells.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cellular Aging

Background:

  • POLD1 (DNA Polymerase Delta catalytic subunit) is crucial for DNA synthesis and repair.
  • POLD1 expression decreases with cellular senescence and aging.
  • Mechanisms underlying age-related POLD1 downregulation remain unclear.

Purpose of the Study:

  • To investigate the molecular mechanisms of age-related POLD1 downregulation.
  • To identify regulatory elements and factors involved in POLD1 expression during aging.

Main Methods:

  • Analysis of CpG islands and methylation patterns in the POLD1 promoter.
  • Investigation of transcription factor E2F1 binding to the POLD1 promoter.
  • Assessment of E2F1 levels and POLD1 promoter methylation effects on binding affinity.
  • Experimental manipulation of E2F1 levels using shRNA to observe senescence phenotypes.

Main Results:

  • Four potential CpG islands were identified in the POLD1 promoter.
  • POLD1 promoter methylation, particularly at CpG 36, increased with cellular age.
  • E2F1 binding affinity to the POLD1 promoter decreased with age.
  • E2F1 levels positively correlated with binding, while promoter methylation showed a negative correlation.
  • Reduced E2F1 levels induced senescence characteristics and contributed to POLD1 downregulation.

Conclusions:

  • Age-related POLD1 downregulation is mediated by decreased E2F1 binding affinity.
  • This attenuation results from both declining E2F1 levels and increased POLD1 promoter methylation.
  • These epigenetic and regulatory changes contribute to cellular aging processes.
Keywords:
DNA methylationE2F1POLD1Replicative senescenceTranscription factor

More Related Videos

Far-Red Fluorescent Senescence-Associated β-Galactosidase Probe for Identification and Enrichment of Senescent Tumor Cells by Flow Cytometry14:01

Far-Red Fluorescent Senescence-Associated β-Galactosidase Probe for Identification and Enrichment of Senescent Tumor Cells by Flow Cytometry

Published on: September 13, 2022

5.7K
Induction and Validation of Cellular Senescence in Primary Human Cells08:18

Induction and Validation of Cellular Senescence in Primary Human Cells

Published on: June 20, 2018

18.0K

Related Concept Videos

Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
4.4K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.8K
Chromosome Replication02:31

Chromosome Replication

Before a cell can divide, it must accurately replicate all of its chromosomes, including the DNA and its associated histone and non-histone proteins.  This process begins at numerous origins of replication during the S phase of the cell cycle in each of a cell’s chromosomes simultaneously. Certain nucleotides can act as origins of replication, but these sequences are not well defined - especially in complex, multi-cellular, eukaryotic species. The length of DNA that spans an origin...
10.6K
DNA Replication02:40

DNA Replication

DNA replication involves the separation of the two strands of the double helix, with each strand serving as a template from which the new complementary strand is copied.  After replication, each double-stranded DNA includes one parental or “old” strand and one “new” strand. This is known as semiconservative replication. The resulting DNA molecules have the same sequence and are divided equally into the two daughter cells.
Replication in Prokaryotes
DNA replication...
59.0K
Replication in Prokaryotes02:35

Replication in Prokaryotes

Overview
97.7K
Replication in Prokaryotes01:32

Replication in Prokaryotes

DNA replication has three main steps: initiation, elongation, and termination. Replication in prokaryotes begins when initiator proteins bind to the single origin of replication (ori) on the cell's circular chromosome. Replication then proceeds around the entire circle of the chromosome in each direction from the two replication forks, resulting in two DNA molecules.
Many Proteins Work Together to Replicate the Chromosome
Replication is coordinated and carried out by a host of specialized...
27.8K