Next Article in Journal
Posttranslational Modifications and Clearing of α-Synuclein Aggregates in Yeast
Next Article in Special Issue
Transcription Blockage Leads to New Beginnings
Previous Article in Journal
Oxidative Stress in Aging Human Skin
Previous Article in Special Issue
Role of the Checkpoint Clamp in DNA Damage Response
Article Menu

Export Article

Open AccessReview
Biomolecules 2015, 5(2), 590-616; doi:10.3390/biom5020590

Protein Degradation Pathways Regulate the Functions of Helicases in the DNA Damage Response and Maintenance of Genomic Stability

1
Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, NIH Biomedical Research Center, 251 Bayview Blvd, Baltimore, MD 21224, USA
2
Department of Medicine, Division of Hematology & Medical Oncology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Wolf-Dietrich Heyer, Thomas Helleday and Fumio Hanaoka
Received: 25 February 2015 / Revised: 9 April 2015 / Accepted: 13 April 2015 / Published: 21 April 2015
(This article belongs to the Special Issue DNA Damage Response)
View Full-Text   |   Download PDF [5311 KB, uploaded 21 April 2015]   |  

Abstract

Degradation of helicases or helicase-like proteins, often mediated by ubiquitin-proteasomal pathways, plays important regulatory roles in cellular mechanisms that respond to DNA damage or replication stress. The Bloom’s syndrome helicase (BLM) provides an example of how helicase degradation pathways, regulated by post-translational modifications and protein interactions with components of the Fanconi Anemia (FA) interstrand cross-link (ICL) repair pathway, influence cell cycle checkpoints, DNA repair, and replication restart. The FANCM DNA translocase can be targeted by checkpoint kinases that exert dramatic effects on FANCM stability and chromosomal integrity. Other work provides evidence that degradation of the F-box DNA helicase (FBH1) helps to balance translesion synthesis (TLS) and homologous recombination (HR) repair at blocked replication forks. Degradation of the helicase-like transcription factor (HLTF), a DNA translocase and ubiquitylating enzyme, influences the choice of post replication repair (PRR) pathway. Stability of the Werner syndrome helicase-nuclease (WRN) involved in the replication stress response is regulated by its acetylation. Turning to transcription, stability of the Cockayne Syndrome Group B DNA translocase (CSB) implicated in transcription-coupled repair (TCR) is regulated by a CSA ubiquitin ligase complex enabling recovery of RNA synthesis. Collectively, these studies demonstrate that helicases can be targeted for degradation to maintain genome homeostasis. View Full-Text
Keywords: helicase; DNA damage response; proteasome; ubiquitin; phosphorylation; acetylation; post-translational modification; Bloom’s syndrome; Fanconi Anemia; Cockayne syndrome; Werner syndrome helicase; DNA damage response; proteasome; ubiquitin; phosphorylation; acetylation; post-translational modification; Bloom’s syndrome; Fanconi Anemia; Cockayne syndrome; Werner syndrome
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Sommers, J.A.; Suhasini, A.N.; Brosh, R.M., Jr. Protein Degradation Pathways Regulate the Functions of Helicases in the DNA Damage Response and Maintenance of Genomic Stability. Biomolecules 2015, 5, 590-616.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Biomolecules EISSN 2218-273X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top