UHRF1 Contributes to DNA Damage Repair as a Lesion Recognition Factor and Nuclease Scaffold

Yanyan Tian; Manikandan Paramasivam; Gargi Ghosal; Ding Chen; Xi Shen; Yaling Huang; Shamima Akhter; Randy Legerski; Junjie Chen; Michael M. Seidman; Jun Qin; Lei Li

doi:10.1016/j.celrep.2015.03.038

Cell Reports (Mar 2015)

UHRF1 Contributes to DNA Damage Repair as a Lesion Recognition Factor and Nuclease Scaffold

Yanyan Tian,
Manikandan Paramasivam,
Gargi Ghosal,
Ding Chen,
Xi Shen,
Yaling Huang,
Shamima Akhter,
Randy Legerski,
Junjie Chen,
Michael M. Seidman,
Jun Qin,
Lei Li

Affiliations

Yanyan Tian: Department of Experimental Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Manikandan Paramasivam: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
Gargi Ghosal: Department of Experimental Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Ding Chen: Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030, USA
Xi Shen: Department of Experimental Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Yaling Huang: Department of Experimental Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Shamima Akhter: Department of Genetics, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Randy Legerski: Department of Genetics, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Junjie Chen: Department of Experimental Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Michael M. Seidman: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
Jun Qin: Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030, USA
Lei Li: Department of Experimental Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

DOI: https://doi.org/10.1016/j.celrep.2015.03.038
Journal volume & issue: Vol. 10, no. 12
pp. 1957 – 1966

Abstract

Read online

We identified ubiquitin-like with PHD and RING finger domain 1 (UHRF1) as a binding factor for DNA interstrand crosslink (ICL) lesions through affinity purification of ICL-recognition activities. UHRF1 is recruited to DNA lesions in vivo and binds directly to ICL-containing DNA. UHRF1-deficient cells display increased sensitivity to a variety of DNA damages. We found that loss of UHRF1 led to retarded lesion processing and reduced recruitment of ICL repair nucleases to the site of DNA damage. UHRF1 interacts physically with both ERCC1 and MUS81, two nucleases involved in the repair of ICL lesions. Depletion of both UHRF1 and components of the Fanconi anemia (FA) pathway resulted in increased DNA damage sensitivity compared to defect of each mechanism alone. These results suggest that UHRF1 promotes recruitment of lesion-processing activities via its affinity to recognize DNA damage and functions as a nuclease recruitment scaffold in parallel to the FA pathway.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

About the journal