What is the DNA repair defect underlying Fanconi anemia?

Research output: Contribution to journalReviewpeer-review

Fanconi anemia (FA) is a rare human genetic disease characterized by bone marrow failure, cancer predisposition, and genomic instability. It has been known for many years that FA patient-derived cells are exquisitely sensitive to DNA interstrand cross-linking agents such as cisplatin and mitomycin C. On this basis, it was widely assumed that failure to repair endogenous interstrand cross-links (ICLs) causes FA, although the endogenous mutagen that generates these lesions remained elusive. Recent genetic evidence now suggests that endogenous aldehydes are the driving force behind FA. Importantly, aldehydes cause a variety of DNA lesions, including ICLs and DNA protein cross-links (DPCs), re-kindling the debate about which DNA lesions cause FA. In this review, we discuss new developments in our understanding of DPC and ICL repair, and how these findings bear on the question of which DNA lesion underlies FA.

Original languageEnglish
JournalCurrent Opinion in Cell Biology
Volume37
Pages (from-to)49-60
Number of pages12
ISSN0955-0674
DOIs
Publication statusPublished - Dec 2015
Externally publishedYes

    Research areas

  • Animals, DNA, DNA Damage, DNA Repair, DNA Replication, Fanconi Anemia, Humans, Journal Article, Research Support, Non-U.S. Gov't, Review

ID: 176967517