Related Experiment Video

Updated: Aug 2, 2026

Advanced Confocal Microscopy Techniques to Study Protein-protein Interactions and Kinetics at DNA Lesions
12:43

Advanced Confocal Microscopy Techniques to Study Protein-protein Interactions and Kinetics at DNA Lesions

Published on: November 12, 2017

Parkin regulates translesion DNA synthesis in response to UV radiation

Xuefei Zhu1, Xiaolu Ma2, Yingfeng Tu1

  • 1State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100101, China.

Oncotarget
|April 22, 2017
PubMed

Insights

Parkin deficiency impairs DNA repair after UV exposure, increasing skin cancer risk in Parkinson's disease patients. This study reveals Parkin's role in maintaining genome stability via DNA repair pathways.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Parkin deficiency is linked to early-onset Parkinson's disease (PD).
  • PD patients have an elevated risk of melanoma and skin tumors, with underlying mechanisms unclear.
  • Parkin's role in DNA damage response and its connection to skin cancer predisposition are not well understood.

Purpose of the Study:

  • To investigate the function of Parkin in maintaining genome stability following ultraviolet (UV) radiation.
  • To elucidate the molecular mechanisms by which Parkin influences DNA repair pathways, particularly translesion DNA synthesis (TLS).
  • To establish a link between Parkin deficiency, impaired DNA repair, and increased susceptibility to skin cancers.

Main Methods:

  • Cell viability and genome stability assays after UV irradiation in Parkin-depleted cells.
  • Analysis of proliferating cell nuclear antigen (PCNA) monoubiquitination and Replication protein A (RPA)-coated single-stranded DNA (ssDNA) formation.
  • Co-immunoprecipitation to assess the interaction between Parkin and NBS1 (Nijmegen breakage syndrome 1).
  • Immunofluorescence to evaluate the recruitment of NBS1 and DNA polymerase eta (Polη) to UV-induced DNA damage sites.
  • Measurement of UV-induced mutagenesis rates.

Main Results:

  • Parkin depletion compromises cell viability and genome stability after UV exposure.
  • Parkin facilitates Rad18-dependent PCNA monoubiquitination by promoting RPA-coated ssDNA formation.
  • Parkin physically interacts with NBS1 and is essential for optimal NBS1 and Polη recruitment to UV damage sites.
  • Parkin deficiency leads to increased UV-induced mutagenesis.

Conclusions:

  • Parkin plays a critical role in protecting genome stability by positively regulating translesion DNA synthesis (TLS) upon UV damage.
  • The findings provide a novel mechanistic link between Parkin deficiency in Parkinson's disease and an increased predisposition to skin cancers.
  • Understanding Parkin's function in DNA repair may offer new therapeutic strategies for PD patients at risk of skin tumors.
Keywords:
ParkinParkinson’s diseasemelanomatranslesion DNA synthesisultraviolet radiation

More Related Videos

Investigation of Protein Recruitment to DNA Lesions Using 405 Nm Laser Micro-irradiation12:29

Investigation of Protein Recruitment to DNA Lesions Using 405 Nm Laser Micro-irradiation

Published on: March 20, 2018

The Lambda Select cII Mutation Detection System07:08

The Lambda Select cII Mutation Detection System

Published on: April 26, 2018

Related Concept Videos

Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
Translesion DNA Polymerases02:10

Translesion DNA Polymerases

Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...