RT Journal Article
T1 FANCD2 Facilitates Replication through Common Fragile Sites.
A1 Madireddy, Advaitha
A1 Kosiyatrakul, Settapong T
A1 Boisvert, Rebecca A
A1 Herrera-Moyano, Emilia
A1 García-Rubio, María L
A1 Gerhardt, Jeannine
A1 Vuono, Elizabeth A
A1 Owen, Nichole
A1 Yan, Zi
A1 Olson, Susan
A1 Aguilera, Andrés
A1 Howlett, Niall G
A1 Schildkraut, Carl L
K1 DNA replication
K1 DNA:RNA hybrids
K1 Fanconi anemia
K1 cancer
K1 common fragile sites
K1 genomic instability
AB Common fragile sites (CFSs) are genomic regions that are unstable under conditions of replicative stress. Although the characteristics of CFSs that render them vulnerable to stress are associated mainly with replication, the cellular pathways that protect CFSs during replication remain unclear. Here, we identify and describe a role for FANCD2 as a trans-acting facilitator of CFS replication, in the absence of exogenous replicative stress. In the absence of FANCD2, replication forks stall within the AT-rich fragility core of CFS, leading to dormant origin activation. Furthermore, FANCD2 deficiency is associated with DNA:RNA hybrid formation at CFS-FRA16D, and inhibition of DNA:RNA hybrid formation suppresses replication perturbation. In addition, we also found that FANCD2 reduces the number of potential sites of replication initiation. Our data demonstrate that FANCD2 protein is required to ensure efficient CFS replication and provide mechanistic insight into how FANCD2 regulates CFS stability.
YR 2016
FD 2016
LK http://hdl.handle.net/10668/10551
UL http://hdl.handle.net/10668/10551
LA en
DS RISalud
RD Apr 10, 2025