In humans there are five RecQ helicases whereas in simpler organisms there are only one. It is of great interest to explore how these RecQ helicases function individually and together and whether there is abundancy of helicase function or whether each play an individual role. There may be circumstances where they can function in a synergistic manner and this would be informative about whether these different RecQ helicases interact with each other and also about the biological importance of certain processes. We and other groups find that the human RecQ helicases participate in DNA repair, and more specifically in certain subpathways of DNA repair. Three of the RecQ helicases are deficient in disorders of premature aging: Werner syndrome, Bloom syndrome and Rothmund Thomson syndrome. Much less is known about the Rothmund-Thomson syndrome protein, RECQ4, and RecQ5 than about the other human RecQ helicases. We find that the RecQ4 protein participates in DNA repair of double and single strand breaks and that cells from individuals with this condition are defective in DNA repair. Biochemically, we are characterizing the RECQ4 protein and while its helicase function in many ways is similar to those of the WRN and BLM helicases, there are also significant differences. Moreover, we are currently exploring potential the protein interactions and protein complexes that RECQ4 participates in. RecQ5 is another member of the RecQ family for which little information is known. We have previously reported that WRN, BLM and RecQ4 can stimulate core base excision repair proteins. Thus we are evaluating whether RecQ5 can also stimulate and interact with BER proteins.
| Lu, Huiming; Shamanna, Raghavendra A; de Freitas, Jessica K et al. (2017) Cell cycle-dependent phosphorylation regulates RECQL4 pathway choice and ubiquitination in DNA double-strand break repair. Nat Commun 8:2039 |
| Lu, Huiming; Shamanna, Raghavendra A; Keijzers, Guido et al. (2016) RECQL4 Promotes DNA End Resection in Repair of DNA Double-Strand Breaks. Cell Rep 16:161-173 |
| Arora, Arvind; Abdel-Fatah, Tarek M A; Agarwal, Devika et al. (2016) Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers. Carcinogenesis 37:63-71 |
| Arora, Arvind; Agarwal, Devika; Abdel-Fatah, Tarek Ma et al. (2016) RECQL4 helicase has oncogenic potential in sporadic breast cancers. J Pathol 238:495-501 |
| Shamanna, Raghavendra A; Lu, Huiming; de Freitas, Jessica K et al. (2016) WRN regulates pathway choice between classical and alternative non-homologous end joining. Nat Commun 7:13785 |
| Shamanna, Raghavendra A; Lu, Huiming; Croteau, Deborah L et al. (2016) Camptothecin targets WRN protein: mechanism and relevance in clinical breast cancer. Oncotarget 7:13269-84 |
| Khadka, Prabhat; Croteau, Deborah L; Bohr, Vilhelm A (2016) RECQL5 has unique strand annealing properties relative to the other human RecQ helicase proteins. DNA Repair (Amst) 37:53-66 |
| Sarkar, Jaya; Wan, Bingbing; Yin, Jinhu et al. (2015) SLX4 contributes to telomere preservation and regulated processing of telomeric joint molecule intermediates. Nucleic Acids Res 43:5912-23 |
| Edwards, Deanna N; Machwe, Amrita; Chen, Li et al. (2015) The DNA structure and sequence preferences of WRN underlie its function in telomeric recombination events. Nat Commun 6:8331 |
| Bürkle, Alexander; Grune, Tilman; Gonos, Efstathios S et al. (2015) Editorial. Mech Ageing Dev 151:1 |
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