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Fanconi anemia proteins and their interacting partners: a molecular puzzle.

Kaddar T, Carreau M - Anemia (2012)

Bottom Line: These other molecular mechanisms may also play an important role in the pathogenesis of this disease.In addition, several FA-interacting proteins have been identified with roles in these "other" nonrepair molecular functions.Thus, the goal of this paper is to revisit old ideas and to discuss protein-protein interactions related to other FA-related molecular functions to try to give the reader a wider perspective of the FA molecular puzzle.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Université Laval, Cité Universitaire, Québec, QC, Canada G1K 7P4.

ABSTRACT
In recent years, Fanconi anemia (FA) has been the subject of intense investigations, primarily in the DNA repair research field. Many discoveries have led to the notion of a canonical pathway, termed the FA pathway, where all FA proteins function sequentially in different protein complexes to repair DNA cross-link damages. Although a detailed architecture of this DNA cross-link repair pathway is emerging, the question of how a defective DNA cross-link repair process translates into the disease phenotype is unresolved. Other areas of research including oxidative metabolism, cell cycle progression, apoptosis, and transcriptional regulation have been studied in the context of FA, and some of these areas were investigated before the fervent enthusiasm in the DNA repair field. These other molecular mechanisms may also play an important role in the pathogenesis of this disease. In addition, several FA-interacting proteins have been identified with roles in these "other" nonrepair molecular functions. Thus, the goal of this paper is to revisit old ideas and to discuss protein-protein interactions related to other FA-related molecular functions to try to give the reader a wider perspective of the FA molecular puzzle.

No MeSH data available.


Related in: MedlinePlus

Putative roles of FA proteins through their interacting partners. The involvement of FA proteins with their protein partners in the different molecular mechanisms that lead to regulation of transcription, cell cycle regulation, ROS detoxification, DNA repair, and cell survival. Loss of protein interactions between FA proteins and their partners through disease causing mutations in a FA gene could lead to a defective molecular function resulting in an array of phenotypes including BMF and congenital malformations.
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fig1: Putative roles of FA proteins through their interacting partners. The involvement of FA proteins with their protein partners in the different molecular mechanisms that lead to regulation of transcription, cell cycle regulation, ROS detoxification, DNA repair, and cell survival. Loss of protein interactions between FA proteins and their partners through disease causing mutations in a FA gene could lead to a defective molecular function resulting in an array of phenotypes including BMF and congenital malformations.

Mentions: Since the discovery of FANCC, the first identified FA gene in 1992 [15], there have been significant advances in the FA molecular biology field. These advances mostly include characterization of the canonical FA pathway, which is activated in response to DNA crosslink damage. It is clear that FA proteins are required for DNA crosslink repair; however, the question of how a defective FA protein leads to BMF, and developmental abnormalities remains elusive. It is obvious that absence of a functional FA protein affects many cellular and molecular functions and leads to an array of cellular phenotypes (see Figure 1). A perplexing question is whether FA proteins interactions with their nonrepair partners act only as modifiers of the clinical manifestation of FA. Once we reconcile all the notions related to FA proteins role in these various cellular and molecular activities, we may then obtain a clearer picture of the complexities of this molecular puzzle.


Fanconi anemia proteins and their interacting partners: a molecular puzzle.

Kaddar T, Carreau M - Anemia (2012)

Putative roles of FA proteins through their interacting partners. The involvement of FA proteins with their protein partners in the different molecular mechanisms that lead to regulation of transcription, cell cycle regulation, ROS detoxification, DNA repair, and cell survival. Loss of protein interactions between FA proteins and their partners through disease causing mutations in a FA gene could lead to a defective molecular function resulting in an array of phenotypes including BMF and congenital malformations.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3378961&req=5

fig1: Putative roles of FA proteins through their interacting partners. The involvement of FA proteins with their protein partners in the different molecular mechanisms that lead to regulation of transcription, cell cycle regulation, ROS detoxification, DNA repair, and cell survival. Loss of protein interactions between FA proteins and their partners through disease causing mutations in a FA gene could lead to a defective molecular function resulting in an array of phenotypes including BMF and congenital malformations.
Mentions: Since the discovery of FANCC, the first identified FA gene in 1992 [15], there have been significant advances in the FA molecular biology field. These advances mostly include characterization of the canonical FA pathway, which is activated in response to DNA crosslink damage. It is clear that FA proteins are required for DNA crosslink repair; however, the question of how a defective FA protein leads to BMF, and developmental abnormalities remains elusive. It is obvious that absence of a functional FA protein affects many cellular and molecular functions and leads to an array of cellular phenotypes (see Figure 1). A perplexing question is whether FA proteins interactions with their nonrepair partners act only as modifiers of the clinical manifestation of FA. Once we reconcile all the notions related to FA proteins role in these various cellular and molecular activities, we may then obtain a clearer picture of the complexities of this molecular puzzle.

Bottom Line: These other molecular mechanisms may also play an important role in the pathogenesis of this disease.In addition, several FA-interacting proteins have been identified with roles in these "other" nonrepair molecular functions.Thus, the goal of this paper is to revisit old ideas and to discuss protein-protein interactions related to other FA-related molecular functions to try to give the reader a wider perspective of the FA molecular puzzle.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Université Laval, Cité Universitaire, Québec, QC, Canada G1K 7P4.

ABSTRACT
In recent years, Fanconi anemia (FA) has been the subject of intense investigations, primarily in the DNA repair research field. Many discoveries have led to the notion of a canonical pathway, termed the FA pathway, where all FA proteins function sequentially in different protein complexes to repair DNA cross-link damages. Although a detailed architecture of this DNA cross-link repair pathway is emerging, the question of how a defective DNA cross-link repair process translates into the disease phenotype is unresolved. Other areas of research including oxidative metabolism, cell cycle progression, apoptosis, and transcriptional regulation have been studied in the context of FA, and some of these areas were investigated before the fervent enthusiasm in the DNA repair field. These other molecular mechanisms may also play an important role in the pathogenesis of this disease. In addition, several FA-interacting proteins have been identified with roles in these "other" nonrepair molecular functions. Thus, the goal of this paper is to revisit old ideas and to discuss protein-protein interactions related to other FA-related molecular functions to try to give the reader a wider perspective of the FA molecular puzzle.

No MeSH data available.


Related in: MedlinePlus