Fanconi anemia: current insights regarding epidemiology, cancer, and DNA repair

Fanconi anemia is a genetic disorder that is characterized by bone marrow failure, as well as a predisposition to malignancies including leukemia and squamous cell carcinoma (SCC). At least 22 genes are associated with Fanconi anemia, constituting the Fanconi anemia DNA repair pathway. This pathway...

Full description

Saved in:
Bibliographic Details
Published in:Human genetics 2022-12, Vol.141 (12), p.1811-1836
Main Authors: Peake, Jasmine D., Noguchi, Eishi
Format: Article
Language:English
Subjects:
Anemia
Biomedical and Life Sciences
Biomedicine
Bone marrow
Cancer
Carcinogens
Chemotherapy
DNA
DNA adducts
DNA biosynthesis
DNA damage
DNA repair
Epidemiology
Fanconi syndrome
Fanconi's anemia
Gene Function
Genetic aspects
Genetic disorders
Genetic transcription
Genomic instability
Health aspects
Human Genetics
Information processing
Leukemia
Malignancy
Metabolic Diseases
Molecular Medicine
Proteins
Review
Reviews
Squamous cell carcinoma
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Fanconi anemia is a genetic disorder that is characterized by bone marrow failure, as well as a predisposition to malignancies including leukemia and squamous cell carcinoma (SCC). At least 22 genes are associated with Fanconi anemia, constituting the Fanconi anemia DNA repair pathway. This pathway coordinates multiple processes and proteins to facilitate the repair of DNA adducts including interstrand crosslinks (ICLs) that are generated by environmental carcinogens, chemotherapeutic crosslinkers, and metabolic products of alcohol. ICLs can interfere with DNA transactions, including replication and transcription. If not properly removed and repaired, ICLs cause DNA breaks and lead to genomic instability, a hallmark of cancer. In this review, we will discuss the genetic and phenotypic characteristics of Fanconi anemia, the epidemiology of the disease, and associated cancer risk. The sources of ICLs and the role of ICL-inducing chemotherapeutic agents will also be discussed. Finally, we will review the detailed mechanisms of ICL repair via the Fanconi anemia DNA repair pathway, highlighting critical regulatory processes. Together, the information in this review will underscore important contributions to Fanconi anemia research in the past two decades.
ISSN:0340-6717
1432-1203
DOI:10.1007/s00439-022-02462-9