Beyond interstrand crosslinks repair: contribution of FANCD2 and other Fanconi Anemia proteins to the replication of DNA.

FEDERICO MB1, CAMPODÓNICO P1, PAVIOLO NS1, GOTTIFREDI V2.

MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2018

0027-5107

Biallelic mutations of FANCD2 and other components of the Fanconi Anemia (FA) pathway cause a disease characterized by bone marrow failure, cancer predisposition and a striking sensitivity to agents that induce crosslinks between the two complementary DNA strands (inter-strand crosslinks-ICL). Such genotoxins were used to characterize the contribution of the FA pathway to the genomic stability of cells, thus unravelling the biological relevance of ICL repair in the context of the disease. Notwithstanding this, whether the defect in ICL repair as the sole trigger for the multiple physiological alterations observed in FA patients is still under investigation. Remarkably, ICL-independent functions of FANCD2 and other components of the FA pathway were recently reported. FANCD2 contributes to the processing of very challenging double strand ends (DSEs: one ended Double Strand Breaks -DSBs- created during DNA replication). Other ICL-independent functions of FANCD2 include prevention of DNA breakage at stalled replication forks and facilitation of chromosome segregation at the end of M phase. The current understanding of replication-associated functions of FANCD2 and its relevance for the survival of genomically stable cells is herein discussed.