Related Experiment Video

Updated: Jan 28, 2026

Immunofluorescence Microscopy of γH2AX and 53BP1 for Analyzing the Formation and Repair of DNA Double-strand Breaks
10:47

Immunofluorescence Microscopy of γH2AX and 53BP1 for Analyzing the Formation and Repair of DNA Double-strand Breaks

Published on: November 3, 2017

17.2K

The nuclear structural protein NuMA is a negative regulator of 53BP1 in DNA double-strand break repair

Naike Salvador Moreno1, Jing Liu2, Karen M Haas3

  • 1Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.

Nucleic Acids Research
|February 28, 2019
PubMed

Insights

P53-binding protein 1 (53BP1) is regulated by NuMA, a structural protein that restrains 53BP1 movement. DNA damage reduces this interaction, impacting DNA repair and potentially tumor treatment responses.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • 53BP1 is crucial for DNA double-strand break repair and checkpoint activation.
  • 53BP1 accumulates at damaged chromatin sites through recognition of specific marks.
  • Regulation of 53BP1 activity extends beyond its presence at DNA repair foci.

Purpose of the Study:

  • To investigate novel regulatory mechanisms of 53BP1.
  • To explore the role of the structural protein NuMA in 53BP1 regulation.
  • To understand the implications of 53BP1-NuMA interaction in DNA repair and cancer.

Main Methods:

  • Studied 53BP1 nucleoplasmic diffusion and its response to DNA damage.
  • Investigated the interaction between 53BP1 and NuMA using in vitro and in vivo models.
  • Analyzed protein colocalization in cell lines and human breast tissues.
  • Assessed the impact of NuMA manipulation on DNA repair pathways and drug sensitivity.

Main Results:

  • 53BP1 nucleoplasmic mobility increases upon DNA damage.
  • NuMA interacts with 53BP1, constraining its diffusion.
  • The 53BP1-NuMA interaction and colocalization decrease after DNA damage.
  • High NuMA expression correlates with better patient outcomes in breast carcinoma.
  • NuMA influences 53BP1-dependent DNA repair and PARP inhibitor sensitivity in BRCA1-null cells.

Conclusions:

  • NuMA sequesters 53BP1 in the nucleoplasm in the absence of DNA damage, potentially disabling repair functions.
  • This NuMA-mediated regulation of 53BP1 is a critical factor in tumor response to genotoxic therapies.
  • Understanding the 53BP1-NuMA interplay offers insights into cancer treatment strategies.

More Related Videos

Analysis of DNA Double-strand Break DSB Repair in Mammalian Cells13:10

Analysis of DNA Double-strand Break DSB Repair in Mammalian Cells

Published on: September 8, 2010

32.7K
Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy08:31

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy

Published on: June 8, 2018

9.6K

Related Concept Videos

Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
14.6K
Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

4.4K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.5K
Overview of DNA Repair02:25

Overview of DNA Repair

In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
33.6K
Mismatch Repair01:36

Mismatch Repair

Overview
43.7K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.3K