TY  - JOUR
A1  - Rohleder, Florian
A1  - Huang, Jing
A1  - Xue, Yutong
A1  - Kuper, Jochen
A1  - Round, Adam
A1  - Seidman, Michael
A1  - Wang, Weidong
A1  - Kisker, Caroline
T1  - FANCM interacts with PCNA to promote replication traverse of DNA interstrand crosslinks
JF  - Nucleic Acids Research
N2  - FANCM is a highly conserved DNA remodeling enzyme that promotes the activation of the Fanconi anemia DNA repair pathway and facilitates replication traverse of DNA interstrand crosslinks. However, how FANCM interacts with the replication machinery to promote traverse remains unclear. Here, we show that FANCM and its archaeal homolog Hef from Thermoplasma acidophilum interact with proliferating cell nuclear antigen (PCNA), an essential co-factor for DNA polymerases in both replication and repair. The interaction is mediated through a conserved PIP-box; and in human FANCM, it is strongly stimulated by replication stress. A FANCM variant carrying a mutation in the PIP-box is defective in promoting replication traverse of interstrand crosslinks and is also inefficient in promoting FANCD2 monoubiquitination, a key step of the Fanconi anemia pathway. Our data reveal a conserved interaction mode between FANCM and PCNA during replication stress, and suggest that this interaction is essential for FANCM to aid replication machines to traverse DNA interstrand crosslinks prior to post-replication repair.
KW  - genome integrity
KW  - repair and replication
KW  - FANCM
KW  - proliferating cell nuclear antigen (PCNA)
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175401
VL  - 44
IS  - 7
ER  -