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

Cellular and Molecular Life Sciences : CMLS
Mariangela SabatellaHannes Lans

Abstract

The effectiveness of many DNA-damaging chemotherapeutic drugs depends on their ability to form monoadducts, intrastrand crosslinks and/or interstrand crosslinks (ICLs) that interfere with transcription and replication. The ERCC1-XPF endonuclease plays a critical role in removal of these lesions by incising DNA either as part of nucleotide excision repair (NER) or interstrand crosslink repair (ICLR). Engagement of ERCC1-XPF in NER is well characterized and is facilitated by binding to the XPA protein. However, ERCC1-XPF recruitment to ICLs is less well understood. Moreover, specific mutations in XPF have been found to disrupt its function in ICLR but not in NER, but whether this involves differences in lesion targeting is unknown. Here, we imaged GFP-tagged ERCC1, XPF and ICLR-defective XPF mutants to investigate how in human cells ERCC1-XPF is localized to different types of psoralen-induced DNA lesions, repaired by either NER or ICLR. Our results confirm its dependence on XPA in NER and furthermore show that its engagement in ICLR is dependent on FANCD2. Interestingly, we find that two ICLR-defective XPF mutants (R689S and S786F) are less well recruited to ICLs. These studies highlight the differential mechanisms that regulate...Continue Reading

References

Feb 1, 1984·Quarterly Reviews of Biophysics·J E HearstK Straub
May 24, 1994·Proceedings of the National Academy of Sciences of the United States of America·L LiR J Legerski
May 24, 1994·Proceedings of the National Academy of Sciences of the United States of America·C H Park, A Sancar
Mar 14, 2000·Molecular and Cellular Biology·D MuA Sancar
Aug 21, 2001·Molecular Cell·M VolkerL H Mullenders
Apr 16, 2002·The EMBO Journal·Jacqueline H Enzlin, Orlando D Schärer
Dec 22, 2006·Nature·Laura J NiedernhoferJan H J Hoeijmakers
Mar 22, 2007·Bioconjugate Chemistry·Arun Kalliat ThazhathveetilMichael M Seidman
Jun 11, 2008·Molecular and Cellular Biology·Anwaar AhmadLaura J Niedernhofer
Mar 13, 2009·The EMBO Journal·Lidija StaresincicOrlando D Schärer
Aug 18, 2009·The Journal of Biological Chemistry·Parameswary A MuniandyMichael M Seidman
Oct 7, 2009·Molecular and Cellular Biology·Nikhil BhagwatPeter J McHugh
Nov 27, 2009·The Journal of Biological Chemistry·Barbara OrelliOrlando D Schärer
Mar 12, 2010·PLoS Genetics·Anwaar AhmadLaura J Niedernhofer
Apr 6, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kimiyo N YamamotoKouji Hirota
Jul 2, 2011·Science·David T LongJohannes C Walter
Sep 8, 2011·Genes & Development·Anderson T WangPeter J McHugh
May 2, 2012·The Journal of Biological Chemistry·Yan SuOrlando D Schärer
Oct 3, 2013·Cold Spring Harbor Perspectives in Biology·Orlando D Schärer
Oct 3, 2013·Cold Spring Harbor Perspectives in Biology·Cheryl ClausonLaura Niedernhofer
May 6, 2014·Journal of Cell Science·Christophe LachaudJohn Rouse
Jun 24, 2014·Nature Reviews. Molecular Cell Biology·Jurgen A MarteijnJan H J Hoeijmakers
Jul 31, 2014·Nature Methods·Neville E SanjanaFeng Zhang
Oct 11, 2014·Nucleic Acids Research·Eva K BrinkmanBas van Steensel
Jul 8, 2015·Nature Communications·Loes van CuijkJurgen A Marteijn
Jun 2, 2016·DNA Repair·Norie SugitaniWalter J Chazin

❮ Previous
Next ❯

Citations

Jul 3, 2021·International Journal of Molecular Sciences·Heling WangEvandro F Fang
Sep 1, 2021·Cellular and Molecular Life Sciences : CMLS·Kazumasa Yoshida, Masatoshi Fujita

❮ Previous
Next ❯

Methods Mentioned

BETA
scraping
Infrared Imaging
dissection
immunoprecipitation
immunoprecipitations
ChIP
fluorescence recovery after photobleaching

Software Mentioned

DEcomposition
Image J

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.