Identification, developmental expression and regulation of the Xenopus ortholog of human FANCG/XRCC9.
Fanconi anemia (FA) is associated with variable developmental abnormalities, bone marrow failure and cancer susceptibility. FANCG/XRCC9 is member of the FA core complex, a group of proteins that control the monoubiquitylation of FANCD2, an event that plays a critical role in maintaining genomic stability. Here we report the identification of the Xenopus laevis ortholog of human FANCG (xFANCG), its expression during development, and its molecular interactions with a partner protein, xFANCA. The xFANCG protein sequence is 47% similar to its human ortholog, with highest conservation in the two putative N-terminal leucine zippers and the tetratricopeptide repeat (TPR) motifs. xFANCG is maternally and zygotically transcribed. Prior to the midblastula stage, a single xFANCG transcript is observed but two additional alternatively spliced mRNAs are detected after the midblastula transition. One of the variants is predicted to encode a novel isoform of xFANCG lacking exon 2. The mutual association between FANCG and FANCA required for their nuclear import is conserved in Xenopus egg extracts. Our data demonstrate that interactions between FANCA and FANCG occur at the earliest stage of vertebrate development and raise the possibility that functionally different isoforms of xFANCG may play a role in early development.
Stone
Stacie
S
Division of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR, USA.
Sobeck
Alexandra
A
van Kogelenberg
Margriet
M
de Graaf
Bendert
B
Joenje
Hans
H
Christian
Jan
J
Hoatlin
Maureen E
ME
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000302:isolation & purification; D004625:Embryo, Nonmammalian; D005091:Exons; D052217:Fanconi Anemia Complementation Group A Protein / Q000378:metabolism; D052241:Fanconi Anemia Complementation Group G Protein / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000302:isolation & purification; D023121:RNA, Messenger, Stored / Q000302:isolation & purification / Q000378:metabolism; D017385:Sequence Homology; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics*
D018076:DNA, Complementary; D052217:Fanconi Anemia Complementation Group A Protein; D052241:Fanconi Anemia Complementation Group G Protein; D020033:Protein Isoforms; D023121:RNA, Messenger, Stored