XPB induces C1D expression to counteract UV-induced apoptosis.
Although C1D has been shown to be involved in DNA double-strand break repair, how C1D expression was induced and the mechanism(s) by which C1D facilitates DNA repair in mammalian cells remain poorly understood. We and others have previously shown that expression of xeroderma pigmentosum B (XPB) protein efficiently compensated the UV irradiation-sensitive phenotype of 27-1 cells, which lack functional XPB. To further explore XPB-regulated genes that could be involved in UV-induced DNA repair, differential display analysis of mRNA levels from CHO-9, 27-1, and 27-1 complemented with wild-type XPB was done and C1D gene was identified as one of the major genes whose expression was significantly upregulated by restoring XPB function. We found that XPB is essential to induce C1D transcription after UV irradiation. The increase in C1D expression effectively compensates for the UV-induced proteolysis of C1D and thus maintains cellular C1D level to cope with DNA damage inflicted by UV irradiation. We further showed that although insufficient to rescue 27-1 cells from UV-induced apoptosis by itself, C1D facilitates XPB DNA repair through direct interaction with XPB. Our findings provided direct evidence that C1D is associated with DNA repair complex and may promote repair of UV-induced DNA damage.
Pediatric Tumor Biology and Ultrastructural Pathology Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-1500, USA. liguan1@mail.nih.gov
Guang
G
Li
Juhong
J
Liu
Mones
M
Abu-Asab
Shibuya
S
Masabumi
Yoshiro
Y
Maru
D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000528:radiation effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D016466:CHO Cells; D056970:Co-Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000528:radiation effects; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage / Q000235:genetics* / Q000528:radiation effects; D004265:DNA Helicases / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D015533:Transcriptional Activation / Q000235:genetics / Q000528:radiation effects; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000235:genetics / Q000528:radiation effects
D051017:Apoptosis Regulatory Proteins; C117400:C1D protein, human; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; C072022:XPBC-ERCC-3 protein; D004265:DNA Helicases