UHRF1 Contributes to DNA Damage Repair as a Lesion Recognition Factor and Nuclease Scaffold
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 cell...
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Elsevier
2015-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715003071 |
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doaj-a43754d290ef40709485288028f50d6a2020-11-24T21:47:27ZengElsevierCell Reports2211-12472015-03-0110121957196610.1016/j.celrep.2015.03.038UHRF1 Contributes to DNA Damage Repair as a Lesion Recognition Factor and Nuclease ScaffoldYanyan Tian0Manikandan Paramasivam1Gargi Ghosal2Ding Chen3Xi Shen4Yaling Huang5Shamima Akhter6Randy Legerski7Junjie Chen8Michael M. Seidman9Jun Qin10Lei Li11Department of Experimental Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USALaboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USADepartment of Experimental Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Biochemistry, Baylor College of Medicine, Houston, TX 77030, USADepartment of Experimental Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Experimental Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Genetics, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Genetics, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Experimental Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USALaboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USADepartment of Biochemistry, Baylor College of Medicine, Houston, TX 77030, USADepartment of Experimental Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAWe 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.http://www.sciencedirect.com/science/article/pii/S2211124715003071 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 UHRF1 Contributes to DNA Damage Repair as a Lesion Recognition Factor and Nuclease Scaffold Cell Reports |
| author_facet |
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 |
| author_sort |
Yanyan Tian |
| title |
UHRF1 Contributes to DNA Damage Repair as a Lesion Recognition Factor and Nuclease Scaffold |
| title_short |
UHRF1 Contributes to DNA Damage Repair as a Lesion Recognition Factor and Nuclease Scaffold |
| title_full |
UHRF1 Contributes to DNA Damage Repair as a Lesion Recognition Factor and Nuclease Scaffold |
| title_fullStr |
UHRF1 Contributes to DNA Damage Repair as a Lesion Recognition Factor and Nuclease Scaffold |
| title_full_unstemmed |
UHRF1 Contributes to DNA Damage Repair as a Lesion Recognition Factor and Nuclease Scaffold |
| title_sort |
uhrf1 contributes to dna damage repair as a lesion recognition factor and nuclease scaffold |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2015-03-01 |
| description |
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. |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124715003071 |
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