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Unformatted text preview: ications for tumorigenesis (Howlett et al., 2005; Langevin et al., 2011; Naim and Rosselli, 2009; Rosado et al.
2011). Here the discovery of a role for FANCD2-Ub in preventing
degradation of nascent DNA strands in vivo independent of ICL
processing complements and extends existing results. Notably
FANCD2-Ub functions epistatically with RAD51 at stalled forks
within this distinct pathway, as does BRCA2, which provides
a more complete understanding of how these proteins maintain
replication fork ﬁdelity in the context of ICL and other DNA
FANCD2 monoubiquitination involves an interaction with the
replisome component proliferating cell nuclear antigen (PCNA
(Howlett et al., 2009). Because BRCA2/RAD51 functionally interacts with FANCD2 (Long et al., 2011; Wang et al., 2004) and
Because of the exquisite sensitivity of FA genes to ICL lesions
BRCA2/RAD51 alone is insufﬁcient for fork protection in the
most studies thus far have focused on their role in ICL repair
absence of FANCD2-Ub, a testable mechanistic model is that
Yet, the FA machinery prevents genome instability and lethality
as part of a protein supercomple...
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This document was uploaded on 02/14/2014.
- Fall '14