Approaches to enhance a repair ability of UV induced DNA damage by promotion of DNA damage-recognition

2013 Fiscal Year Final Research Report

• Project/Area Number: 24651052
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Nara Medical University
• Principal Investigator: SUGIURA Shigeki 奈良県立医科大学, 医学部, 准教授 (40179130)
• Co-Investigator(Kenkyū-buntansha): MORI Toshio 奈良県立医科大学, 医学部, 研究教授 (10115280)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 修復 / DNA 損傷 / ｼｸﾛﾌﾞﾀﾝ 型 ﾀﾞｲﾏｰ / ﾓﾉｸﾛｰﾅﾙ 抗体

Research Abstract

Cyclobutane pyrimidine dimers (CPDs) is one of the major types of DNA damage induced by solar UV and is repaired exclusively by a nucleotide excision repair system (NER) in humans. The efficiency of NER mostly depends on helix-distortion of DNA lesion. Therefore, increasing the helix-distortion by CPDs may enhance NER efficiency. We cloned VH and VL genes of anti-CPDs antibody and constructed a single-chain Fv (ScFv) containing C-terminal SV40 nulear localization signal. The binding affinity of the scFv for CPDs was significantly lower than that of original IgG. Then we constructed a Fab containing C-terminal SV40 NLS. It effectively bound to CPDs.

Research Products

• [Journal Article] Quantitative and in situ detection of oxidatively generated DNA damage 8,5'-Cyclo-2'deoxyadenosine using an immunoassay with a novel monoclonal antibody (2014)
  • Author(s): Iwamoto, T., Brooks, P. J., Nishiwaki, T., Nishimura, K., Kobayashi, N., Sugiura, S., and Mori, T.
  • Journal Title: Photochem. Photobiol.
  • DOI: 10.1111/php.12239
  • Peer Reviewed
• [Journal Article] THF-alpha stimulates efficient JC virus replication in neuroblastoma cells (2014)
  • Author(s): Nukuzuma, S., Nakamichi, K., Kameoka, M., Sugiura, S., Nukuzuma, C., Tasaki, T., and Takegami, T.
  • Journal Title: J. Med. Virol.
  • DOI: 10.1002/jmv.23886
  • Peer Reviewed
• [Journal Article] Suppressive effect oh PARP-1 inhibitor on JC virus replication in vitro (2013)
  • Author(s): Nukuzuma, S., Kameoka, M., Sugiura, S., Nakamichi, K., Nukuzuma, C., and Takegami, T.
  • Journal Title: J. Med. Virol. Volume: 85 Pages: 132-137
  • DOI: 10.1002/jmv23443
  • Peer Reviewed
• [Journal Article] Exogenious human immunodeficiency virus-1 protein, Tat, enhances replication of JC virus efficiently in neuroblastoma cell lines (2012)
  • Author(s): Nukuzuma, S., Kameoka, M., Sugiura, S., Nakamichi, K., Nukuzuma, C., Miyoshi, I., and Takegami, T.
  • Volume: 84
  • Pages: 555-561
  • DOI: 10.1002/jmv.23239
  • Peer Reviewed
• [Presentation] Quantitative and in situ detection of oxidatively generated DNA damage 8,5'-Cyclo-2'deoxyadenosine using an immunoassay with a novel monoclonal antibody (2014)
  • Author(s): Iwamoto, T., Brooks, P. J., Kobayashi, N., Sugiura, S., and Mori, T.
  • Organizer: International symposium on xeroderma pigmentosum and related diseases : Disorderes of DNA damage response-Bench to -bedside-
  • Place of Presentation: Kobe
  • Year and Date: 20140305-07
• [Presentation] PARP-1阻害剤のin vitroにおけるウイルス増殖抑制効果について (2013)
  • Author(s): 奴久妻聡一、亀岡正典、杉浦重樹、中道一生、奴久妻智代子、田崎隆史、竹上勉
  • Organizer: 日本ウイルス学会
  • Place of Presentation: 神戸
  • Year and Date: 20131110-12
• [Presentation] HIV-1 Tatによる神経芽細胞腫でのJCウイルス増殖促進 (2012)
  • Author(s): 奴久妻聡一、亀岡正典、杉浦重樹、中道一生、奴久妻智代子、竹上勉
  • Organizer: 日本ウイルス学会
  • Place of Presentation: 大阪
  • Year and Date: 20121113-15