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Malfunction of Nuclease ERCC1-XPF Results in Diverse Clinical Manifestations and Causes Cockayne Syndrome, Xeroderma Pigmentosum, and Fanconi Anemia

Research Project

Project/Area Number 24790321
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pathological medical chemistry
Research InstitutionNagasaki University

Principal Investigator

NAKAZAWA Yuka  長崎大学, 原爆後障害医療研究所, 助教 (00533902)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
KeywordsDNA修復 / ヌクレオチド除去修復 / 分子遺伝子診断学 / DNA損傷修復
Outline of Final Research Achievements

Nucleotide excision repair (NER) removes sunlight-induced photolesions from DNA. There are several NER-deficient human disorders: Cockayne syndrome (CS) is characterised by developmental abnormalities as well as sun-sensitivity, while xeroderma pigmentosum (XP) is associated with skin cancer predisposition. UV-sensitive syndrome (UVSS) patients only display mild skin photosensitivity.
We have previously identified 12 CS-patients who did not have mutations in any of known CS-genes. In this research, we further analysed the CS-cases and characterise three CS patients deficient in ERCC1 or ERCC4 (XPF) genes. Interestingly, one of these patients with mutations in XPF had clinical features of CS, XP, and Fanconi anemia (FA). Our results indicate a multifunctional role for the ERCC1-XPF endonuclease.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (15 results)

All 2015 2014 2013 2012 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) Remarks (2 results)

  • [Journal Article] A rapid, comprehensive system for assaying DNA repair activity and cytotoxic effects of DNA-damaging reagents.2015

    • Author(s)
      Nan Jia, Yuka Nakazawa, Chaowan Guo, Mayuko Shimada, Mieran Sethi, Yoshito Takahashi, Hiroshi Ueda, Yuji Nagayama, Tomoo Ogi
    • Journal Title

      Nature Protocols

      Volume: 10 Issue: 1 Pages: 12-24

    • DOI

      10.1038/nprot.2014.194

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Hypomorphic PCNA mutation underlies a human DNA repair disorder.2014

    • Author(s)
      Baple EL, Chambers H, Cross HE, Fawcett H, Nakazawa Y, Chioza BA, Harlalka GV, Mansour S, Sreekantan-Nair A, Patton MA, Muggenthaler M, Rich P, Wagner K, Coblentz R, Stein CK, Last JI, Taylor AM, Jackson AP, Ogi T, Lehmann AR, Green CM, Crosby AH.
    • Journal Title

      Journal of Clinical Investigation

      Volume: 124 Issue: 7 Pages: 3137-3146

    • DOI

      10.1172/jci74593

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Malfunction of Nuclease ERCC1-XPF Results in Diverse Clinical Manifestations and Causes Cockayne Syndrome, Xeroderma Pigmentosum, and Fanconi Anemia.2013

    • Author(s)
      Kashiyama, K, Nakazawa, Y, Pilz, DT, Guo, C, Sasaki, K, et al.
    • Journal Title

      The American Journal of Human Genetics

      Volume: 92 Issue: 5 Pages: 807-819

    • DOI

      10.1016/j.ajhg.2013.04.007

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel syndrome2012

    • Author(s)
      *Ogi T , Walker S, Stiff T, Hobson E, Limsirichaikul S, Carpenter G, Prescott K, Suri M, Byrd P, Matsuse M, Mitsutake N, Nakazawa Y, Vasudevan P, Barrow M, Stewart G, Taylor M, O'Driscoll M, and Jeggo P
    • Journal Title

      PLoS Genetics

      Volume: 8 Issue: 11 Pages: e1002945-e1002945

    • DOI

      10.1371/journal.pgen.1002945

    • NAID

      120006985789

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair2012

    • Author(s)
      Nakazawa Y, Sasaki K, Mitsutake N, Yamashita S, Ogi T, et al
    • Journal Title

      Nat Genet

      Volume: 44(5) Issue: 5 Pages: 586-92

    • DOI

      10.1038/ng.2229

    • NAID

      120006985586

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 放射線感受性および各種発達異常を示す遺伝性疾患の新規責任遺伝子の同定と分子機能解析2014

    • Author(s)
      中沢由華、郭朝万、嶋田繭子、宮崎仁美、唐田清伸、荻朋男
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Molecular and functional study on the initiation of transcription coupled nucleo tide excision repair2014

    • Author(s)
      Guo C, Nakazawa Y, Shimada M, Jia N, Karata K, Miyazaki H, Ogi T.
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] コケイン症候群様の臨床症状を示す遺伝性疾患の責任遺伝子探索2014

    • Author(s)
      宮崎仁美、中沢由華、郭朝万、嶋田繭子、賈楠、唐田清伸、荻朋男
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] エキソーム解析を用いたDNA修復機構欠損性疾患の新規責任遺伝子の探索2014

    • Author(s)
      嶋田繭子、中沢由華、郭朝万、賈楠、宮崎仁美、唐田清伸、荻朋男
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] ERCC1/XPF deficiency causes three NER- deficient disorders: a patient with various symptoms of xeroderma pigmentosum, Cockayne syndrome & Fanconi anemia.2014

    • Author(s)
      Nakazawa Y, Kashiyama K, Pilz DT, Guo C, Shimada M, Sasaki K, Fawcett H, Wing JF, Lewin SO, Carr L, Li TS, Yoshiura K, Utani A, Hirano A, Greenblatt D, Nardo T, Stefanini M, McGibbon D, Sarkany R, Fassihi H, Mitsutake N, Lehmann AR, Ogi T.
    • Organizer
      The 9th 3R Symposium
    • Place of Presentation
      御殿場高原ホテル(静岡県御殿場市)
    • Year and Date
      2014-11-17 – 2014-11-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] Molecular characterization and functional analysis of XRCC4, a novel pathological gene for radiation sensitivity and developmental abnormalities2014

    • Author(s)
      Guo C, Nakazawa Y, Shimada M, Woodbine L, Jia N, Karata K, Miyazaki H, Lehmann A, Jeggo PA, Ogi T.
    • Organizer
      The 9th 3R Symposium
    • Place of Presentation
      御殿場高原ホテル(静岡県御殿場市)
    • Year and Date
      2014-11-17 – 2014-11-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] Malfunction of Nuclease ERCC1-XPF Results in Diverse Clinical Manifestations and Causes Cockayne Syndrome, Xeroderma Pigmentosum, and Fanconi Anemia2013

    • Author(s)
      中沢由華
    • Organizer
      11th International Conference on Environmental Mutagens
    • Place of Presentation
      Bourbon Convention & Spa Resort Cataratas do Iguassu(ブラジル)
    • Related Report
      2013 Research-status Report
  • [Presentation] RNA polymerase processing in nucleotide-excision-repair-deficient genetic disorders

    • Author(s)
      中沢 由華
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡市
    • Related Report
      2012 Research-status Report
  • [Remarks] 長崎大学 がん・ゲノム不安定性研究拠点ホームページ

    • URL

      http://www.nrgic.prj.nagasaki-u.ac.jp/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 長崎大学 がん・ゲノム不安定性研究拠点ホームページ

    • URL

      http://www.nrgic.prj.nagasaki-u.ac.jp/

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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