How Fanconi anemia (FA) protein D2 (FANCD2) performs DNA damage repair remains largely elusive. We report here that translesion synthesis DNA polymerase (pol) eta is a novel mediator of FANCD2 function. We found that wild type (wt) FANCD2, not K561R (mt) FANCD2, can interact with pol eta. Upon DNA damage, the interaction of pol eta with FANCD2 occurs earlier than that with PCNA, which is in concert with our finding that FANCD2 monoubiquitination peaks at an earlier time point than that of PCNA monoubiquitination. FANCD2-null FA patient cells (PD20) carrying histone H2B-fused pol eta and wtFANCD2, respectively, show a similar tendency of low Mitomycin C (MMC) sensitivity, while cells transfected with empty vector control or pol eta alone demonstrate a similar high level of MMC sensitivity. It therefore appears that FANCD2 monoubiquitination plays a similar anchor role as histone to bind DNA in regulating pol eta. Collectively, our study indicates that, in the early phase of DNA damage response, FANCD2 plays crucial roles in recruiting pol eta to the sites of DNA damage for repair.
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| http://dx.doi.org/10.4161/cc.23755 | DOI Listing |
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The replicative polymerase delta is inefficient copying repetitive DNA sequences. Error-prone translesion polymerases have been shown to switch with high-fidelity replicative polymerases to help navigate repetitive DNA. We and others have demonstrated the importance of one such translesion polymerase, polymerase Eta (pol eta), in facilitating replication at genomic regions called common fragile sites (CFS), which are difficult-to-replicate genomic regions that are hypersensitive to replication stress.
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Article Synopsis
- Survivin plays a crucial role in inhibiting apoptosis and aiding mitotic progression, as well as contributing to therapy resistance through its involvement in the DNA damage response.
- Recent research shows that ionizing radiation increases Survivin levels, leading to its accumulation in specific nuclear areas associated with DNA replication, and depletion of Survivin enhances DNA damage markers, suggesting a role in DNA repair.
- The study uncovers a relationship between Survivin and chromosomal passenger complex proteins in facilitating damage-induced replication stress management, highlighting the potential for these proteins to influence tumorigenesis due to their overexpression in cancers.
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