Journal
MOLECULAR CELL
Volume 58, Issue 6, Pages 1090-1100Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2015.05.013
Keywords
-
Categories
Funding
- NIH grant [R01 ES016486]
- Vanderbilt Center in Molecular Toxicology [P30 ES000267]
- American Cancer Society fellowship [PF-12-156-01-DMC]
- NIH training grant in Tumor Biology [T32 CA09151]
- Vanderbilt Molecular Biophysics Training Program [NIH T32 GM08320]
- Regenerative Medicine Research Fund [13-SCA-UCHC-03]
- Connecticut Department of Public Health Biomedical Research Fund [2013-0203]
- University of Connecticut Summer Undergraduate Research Fund (SURF)
- US DOE [DE-AC02-06CH11357]
- Michigan Economic Development Corporation
- Michigan Technology Tri-Corridor [085P1000817]
Ask authors/readers for more resources
Stalled replication forks are a critical problem for the cell because they can lead to complex genome rear-rangements that underlie cell death and disease. Processes such as DNA damage tolerance and replication fork reversal protect stalled forks from these events. A central mediator of these DNA damage responses in humans is the Rad5-related DNA translocase, HLTF. Here, we present biochemical and structural evidence that the HIRAN domain, an ancient and conserved domain found in HLTF and other DNA processing proteins, is a modified oligonucleotide/oligosaccharide (OB) fold that binds to 3' ssDNA ends. We demonstrate that the HIRAN domain promotes HLTF-dependent fork reversal in vitro through its interaction with 3' ssDNA ends found at forks. Finally, we show that HLTF restrains replication fork progression in cells in a HIRAN-dependent manner. These findings establish a mechanism of HLTF-mediated fork reversal and provide insight into the requirement for distinct fork remodeling activities in the cell.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available