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

2014 Fiscal Year Final Research Report

• Project/Area Number: 24790321
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Nagasaki 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
• Keywords: DNA修復 / ヌクレオチド除去修復

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.

Free Research Field

病態医化学