Related Experiment Video

Updated: Jan 21, 2026

Single Molecule Analysis of Laser Localized Psoralen Adducts
11:46

Single Molecule Analysis of Laser Localized Psoralen Adducts

Published on: April 20, 2017

7.0K

ERCC1-XPF targeting to psoralen-DNA crosslinks depends on XPA and FANCD2

Mariangela Sabatella1,2, Alex Pines1,2, Jana Slyskova1,3

  • 1Department of Molecular Genetics, Erasmus MC, 3015 GE, Rotterdam, The Netherlands.

Cellular and Molecular Life Sciences : CMLS
|August 9, 2019
PubMed

Insights

The ERCC1-XPF endonuclease repairs DNA damage from chemotherapy drugs. Its recruitment to interstrand crosslinks (ICLs) depends on FANCD2, and specific mutations impair this targeting.

Area of Science:

  • Molecular Biology
  • DNA Repair Mechanisms
  • Cancer Therapeutics

Background:

  • Chemotherapeutic drugs induce DNA damage, including interstrand crosslinks (ICLs), which are critical targets for cancer treatment.
  • The ERCC1-XPF endonuclease is essential for repairing DNA lesions via nucleotide excision repair (NER) and ICL repair (ICLR).
  • While ERCC1-XPF's role in NER is understood, its recruitment to ICLs and the impact of specific mutations on its targeting remain unclear.

Purpose of the Study:

  • To investigate the localization of ERCC1-XPF and its mutants to psoralen-induced DNA lesions repaired by NER or ICLR in human cells.
  • To elucidate the differential mechanisms regulating ERCC1-XPF activity in distinct DNA repair pathways.

Main Methods:

  • Utilized GFP-tagged ERCC1, XPF, and ICLR-defective XPF mutants for live-cell imaging.
  • Visualized the localization of these proteins to psoralen-induced DNA lesions.
  • Analyzed the dependence of ERCC1-XPF recruitment on XPA for NER and FANCD2 for ICLR.

Main Results:

  • Confirmed ERCC1-XPF dependence on XPA for NER.
  • Demonstrated that ERCC1-XPF engagement in ICLR is dependent on FANCD2.
  • Showed that two ICLR-defective XPF mutants (R689S and S786F) exhibit reduced recruitment to ICLs.

Conclusions:

  • ERCC1-XPF localization and function are differentially regulated in NER and ICLR pathways.
  • FANCD2 is crucial for recruiting ERCC1-XPF to ICLs, highlighting a distinct mechanism from NER.
  • Specific XPF mutations affecting ICLR also impair its targeting to ICLs, suggesting a link between recruitment and repair efficiency.
Keywords:
DNA damage responseDNA repairFanconi anemiaXeroderma pigmentosum–Cockayne syndrome complex

More Related Videos

Mapping RNA-RNA Interactions Globally Using Biotinylated Psoralen11:32

Mapping RNA-RNA Interactions Globally Using Biotinylated Psoralen

Published on: May 24, 2017

12.6K
Preparation of DNA-crosslinked Polyacrylamide Hydrogels09:06

Preparation of DNA-crosslinked Polyacrylamide Hydrogels

Published on: August 27, 2014

15.2K

Related Concept Videos

Frequency-dependent Selection01:21

Frequency-dependent Selection

When the fitness of a trait is influenced by how common it is (i.e., its frequency) relative to different traits within a population, this is referred to as frequency-dependent selection. Frequency-dependent selection may occur between species or within a single species. This type of selection can either be positive—with more common phenotypes having higher fitness—or negative, with rarer phenotypes conferring increased fitness.
23.1K
DNA-only Transposons02:57

DNA-only Transposons

DNA-only transposons are called autonomous transposons since they code for the enzyme transposase that is required for the transposition mechanism. Insertion of transposons can alter gene functions in multiple ways. They can mutate the gene, alter gene expression by introducing a novel promoter or insulator sequence, introduce new splice sites, and change the mRNA transcripts produced, or remodel chromatin structure.
The donor site from where the transposon is excised is either degraded or...
17.3K
DNA Topoisomerases02:02

DNA Topoisomerases

Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
35.1K
DNA Packaging00:58

DNA Packaging

Overview
112.1K
Drug Dependence01:17

Drug Dependence

Medications are typically administered to achieve therapeutic effects. Some drugs can modify an individual's mood and perception, frequently resulting in various enjoyable experiences. However, this can result in drug dependency, a condition marked by continuous drug use despite potential negative consequences. Drug dependency primarily falls into two categories: psychological and physical dependence. Psychological dependence occurs when the pleasurable feelings induced by the drug...
1.6K
Contact-dependent Signaling01:19

Contact-dependent Signaling

Contact-dependent signaling, as the name suggests, requires that communicating cells be in direct contact with each other. This is achieved either through receptor-ligand interactions or by specialized cytoplasmic channels that allow the flow of small molecules between cells. In animal cells, channels called gap junctions facilitate contact-dependent signaling in certain tissues, whereas, plasmodesmata perform a similar function in plants.
Gap Junctions
In animal cells, gap junctions are formed...
46.9K