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Review
. 2017 Aug 19;18(8):1804.
doi: 10.3390/ijms18081804.

FANCD2 and DNA Damage

Manoj Nepal  1   2 , Raymond Che  3   4 , Chi Ma  5 , Jun Zhang  6 , Peiwen Fei  7   8
Affiliations
Review

FANCD2 and DNA Damage

Manoj Nepal et al. Int J Mol Sci. .

Abstract

Investigators have dedicated considerable effort to understanding the molecular basis underlying Fanconi Anemia (FA), a rare human genetic disease featuring an extremely high incidence of cancer and many congenital defects. Among those studies, FA group D2 protein (FANCD2) has emerged as the focal point of FA signaling and plays crucial roles in multiple aspects of cellular life, especially in the cellular responses to DNA damage. Here, we discuss the recent and relevant studies to provide an updated review on the roles of FANCD2 in the DNA damage response.

Keywords: DNA damage repair; FANCD2; Fanconi anemia; cancer and aging; checkpoint.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Outline of FA group D2 protein (FANCD2) functions under stressed conditions. In stressed cells, ataxia telangiectasia and Rad3-related protein (ATR) or ataxia telangiectasia mutated (ATM) is activated upon the generation of DNA single or double strand breaks (SSB or DSB), respectively. FANCD2 activation/monoubiquitination issued from the Fanconi anemia (FA) core complex E3 and an E2 (FANCT) can be promoted by the phosphorylation of FANCI triggered by activated ATR, thus conducting important roles that have originated from the activation of ATR. FANCD2 can also play roles not only in aiding ATM signaling for S phase arrest through ATM-dependent phosphorylation at S222 but also possibly in facilitating the initiation of ATM signaling far more upstream via its involvement in the phosphorylation of H2AX. Furthermore, human homologs of yeast Rad6 (HHR6) & hRad18 are also capable of regulating the functions of FANCD2, together influencing the functions of the downstream partners of FANCD2, including Fanconi-associated nuclease 1 (FAN1), DNA polymerase eta (Pol eta), and many others known or yet to be identified.
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