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

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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 invivo 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.

Original languageEnglish (US)
Pages (from-to)1957-1966
Number of pages10
JournalCell Reports
Volume10
Issue number12
DOIs
StatePublished - Mar 31 2015

Fingerprint

Scaffolds
DNA Repair
DNA Damage
Repair
Fanconi Anemia
DNA
RING Finger Domains
Ubiquitin
Processing
Purification
Defects

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

UHRF1 contributes to DNA damage repair as a lesion recognition factor and nuclease scaffold. / Tian, Yanyan; Paramasivam, Manikandan; Ghosal, Gargi; Chen, Ding; Shen, Xi; Huang, Yaling; Akhter, Shamima; Legerski, Randy; Chen, Junjie; Seidman, Michael M.; Qin, Jun; Li, Lei.

In: Cell Reports, Vol. 10, No. 12, 31.03.2015, p. 1957-1966.

Research output: Contribution to journalArticle

Tian, Y, Paramasivam, M, Ghosal, G, Chen, D, Shen, X, Huang, Y, Akhter, S, Legerski, R, Chen, J, Seidman, MM, Qin, J & Li, L 2015, 'UHRF1 contributes to DNA damage repair as a lesion recognition factor and nuclease scaffold', Cell Reports, vol. 10, no. 12, pp. 1957-1966. https://doi.org/10.1016/j.celrep.2015.03.038
Tian, Yanyan ; Paramasivam, Manikandan ; Ghosal, Gargi ; Chen, Ding ; Shen, Xi ; Huang, Yaling ; Akhter, Shamima ; Legerski, Randy ; Chen, Junjie ; Seidman, Michael M. ; Qin, Jun ; Li, Lei. / UHRF1 contributes to DNA damage repair as a lesion recognition factor and nuclease scaffold. In: Cell Reports. 2015 ; Vol. 10, No. 12. pp. 1957-1966.
@article{66124d7bd87b4a6b923d7cb43f8beb09,
title = "UHRF1 contributes to DNA damage repair as a lesion recognition factor and nuclease scaffold",
abstract = "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 invivo 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.",
author = "Yanyan Tian and Manikandan Paramasivam and Gargi Ghosal and Ding Chen and Xi Shen and Yaling Huang and Shamima Akhter and Randy Legerski and Junjie Chen and Seidman, {Michael M.} and Jun Qin and Lei Li",
year = "2015",
month = "3",
day = "31",
doi = "10.1016/j.celrep.2015.03.038",
language = "English (US)",
volume = "10",
pages = "1957--1966",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "12",

}

TY - JOUR

T1 - UHRF1 contributes to DNA damage repair as a lesion recognition factor and nuclease scaffold

AU - Tian, Yanyan

AU - Paramasivam, Manikandan

AU - Ghosal, Gargi

AU - Chen, Ding

AU - Shen, Xi

AU - Huang, Yaling

AU - Akhter, Shamima

AU - Legerski, Randy

AU - Chen, Junjie

AU - Seidman, Michael M.

AU - Qin, Jun

AU - Li, Lei

PY - 2015/3/31

Y1 - 2015/3/31

N2 - 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 invivo 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.

AB - 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 invivo 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.

UR - http://www.scopus.com/inward/record.url?scp=84925956835&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925956835&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2015.03.038

DO - 10.1016/j.celrep.2015.03.038

M3 - Article

VL - 10

SP - 1957

EP - 1966

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 12

ER -