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The Fanconi anemia ID2 complex: dueling saxes at the crossroads.

ABSTRACT: Fanconi anemia (FA) is a rare recessive genetic disease characterized by congenital abnormalities, bone marrow failure and heightened cancer susceptibility in early adulthood. FA is caused by biallelic germ-line mutation of any one of 16 genes. While several functions for the FA proteins have been ascribed, the prevailing hypothesis is that the FA proteins function cooperatively in the FA-BRCA pathway to repair damaged DNA. A pivotal step in the activation of the FA-BRCA pathway is the monoubiquitination of the FANCD2 and FANCI proteins. Despite their importance for DNA repair, the domain structure, regulation, and function of FANCD2 and FANCI remain poorly understood. In this review, we provide an overview of our current understanding of FANCD2 and FANCI, with an emphasis on their posttranslational modification and common and unique functions.

SUBMITTER: Boisvert RA

PROVIDER: S-EPMC4612647 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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The Fanconi anemia ID2 complex: dueling saxes at the crossroads.

Boisvert Rebecca A RA Howlett Niall G NG

Cell cycle (Georgetown, Tex.) 20140101 19

Fanconi anemia (FA) is a rare recessive genetic disease characterized by congenital abnormalities, bone marrow failure and heightened cancer susceptibility in early adulthood. FA is caused by biallelic germ-line mutation of any one of 16 genes. While several functions for the FA proteins have been ascribed, the prevailing hypothesis is that the FA proteins function cooperatively in the FA-BRCA pathway to repair damaged DNA. A pivotal step in the activation of the FA-BRCA pathway is the monoubiqu ...[more]

PMID: 25486561

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Modularized functions of the Fanconi anemia core complex.

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Mutated Fanconi anemia pathway in non-Fanconi anemia cancers.

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Fanconi anemia core complex gene promoters harbor conserved transcription regulatory elements.

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Modern management of Fanconi anemia.

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Uncoupling of transcription and translation of Fanconi anemia (FANC) complex proteins during spermatogenesis.

Project description:Male germ cell genome integrity is critical for spermatogenesis, fertility and normal development of the offspring. Several DNA repair pathways exist in male germ cells. One such important pathway is the Fanconi anemia (FANC) pathway. Unlike in somatic cells, expression profiles and the role of the FANC pathway in germ cells remain largely unknown. In this study, we undertook an extensive expression analyses at both mRNA and protein levels of key components of the FANC pathway during spermatogenesis in the mouse. Herein we show that Fanc mRNAs and proteins displayed developmental enrichment within particular male germ cell types. Spermatogonia and pre-leptotene spermatocytes contained the majority of the FANC components examined i.e. complex I members FANCB, FANCG and FANCM, complex II members FANCD2 and FANCI, and complex III member FANCJ. Leptotene, zygotene and early pachytene spermatocytes contained FANCB, FANCG, FANCM and FANCD2. With the exception of FANCL, all FANC proteins examined were not detected in round spermatids. Elongating and elongated spermatids contained FANCB, FANCG, FANCL and FANCJ. qPCR analysis on isolated spermatocytes and round spermatids showed that Fancg, Fancl, Fancm, Fancd2, Fanci and Fancj mRNAs were expressed in both of these germ cell types, indicating that some degree of translational repression of these FANC proteins occurs during the transition from meiosis to spermiogenesis. Taken together, our findings raise the possibility that the assembly of FANC protein complexes in each of the male germ cell type is unique and may be distinct from the proposed model in mitotic cells.

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