RecQ helicase

Hickson ID (2003) RecQ helicases caretakers of the genome. Nat Rev Cancer 3 169-178 Hirano K, Miki Y, Hirai Y, Sato R, Itoh T, Hayashi A, Yamanaka M, Eda S, Beppu M (2005) A multifunctional shuttling protein nucleolin is a macrophage receptor for apoptotic cells. J Biol Chem... 

E. coli Recq helicase catalytic core lOYW Cysa 2 CySba 2 Cys 16 Cysba (N)... 

Ellis NA, Groden J, Ye TZ, Straughen J, Lennon DJ, et al. 1995. The Bloom s syndrome gene product is homologous to RecQ helicases. Cell 83 655-66... 

G-quadruplex ligands from the trisubstituted acridine series were also found to inhibit in vitro the unwinding by the RecQ helicases, BLM and WRN. Therefore, because of their additional effects on RecQ helicases, these ligands should also disrupt telomere synthesis (Figure 11). In addition, their action against other G-quadruplex resolvases during replication might provoke DNA... 

The RecQ helicases comprise a small, conserved enzyme family which is essential for maintenance of genomic stability in organisms from E. coli to human. " There is only one RecQ family member in E. coli (RecQ), one in S. cerevisiae (Sgsl), one in S. pombe (Rqhl), and five in Homo sapiens. Three human members of the RecQ family are associated with genomic instability and predisposition to malignancies WRN with Werner s syndrome, BLM with Bloom s syndrome, and RTS (or RECQ4) with Rothmund-Thompson syndrome. RecQ helicases are unusual in their ability to unwind G4 DNA, " ... 

The possibility that the human RecQ helicase, WRN, may function to maintain telomeres has drawn considerable attention because premature aging is the hallmark of Werner syndrome. Afiected individuals develop normally until their teens, then rapidly develop characteristics of aging, including graying hair, alopecia, osteoporosis, type II diabetes and cataracts, and premature death, at an average age of 40. This is accompanied by chromosomal instability and cancer. 

Finally a number of gioups recendy came up with an intriguing new aspect of the link between PARP-1 and aging There are a few rare genedc disorders that induce premature aging in humans. One of these examples is Werner syndrome, due to mutation in the WPiNgput. The WRN gene encodes the WRN protein, a member of the RecQ helicase family which comprises an additional exonudease activity. WRN is part of the DNA replication complex and cooperates with several replication- and repair-relat proteins. Recendy, it was shown... 

Sarlos K, Gyimesi M, Kovacs M. RecQ helicase translocates along single-stranded DNA with a moderate processivity and tight mechanochemical coupling. Proc Natl Acad Sci USA. 2012 Jun 4 doi 10.1073/pnas. 1114468.109. 

Raymond J, Monnat JAR. Human RECQ helicase roles in DNA metabolism, mutagenesis and cancer biology. Semin Cancer Biol. 2010 20 329-39. 

The winding of DNA in higher-order forms such as knots and catenanes was also shown in electron micrographs of DNA molecules coated with Escherichia coli RecA protdn. It was found that DNA topoisomerase I of E. coli generates an equal mixture of (+) and (-) duplex DNA knots, and that one product was a catenane. It was later shown that RecQ helicase and topoisomerase III (Topo III) of E. coli together mediate a potent DNA strand passage activity that can catenate covalendy dosed DNA." The structure of the catenated DNA spedes formed by... 

RecQ helicase and Topo III was then direaly assessed by AFM. Images show complex catenated DNA species involving crossovers between multiple double-stranded DNA molecules that are consistent with full catenanes. ... 

Exonuclease domain fused to RecQ-type helicase domain in Werner syndrome protein (WRNp) (Moser et al., 1997 Mushegian et al., 1997)... 

Cells of patients with Bloom syndrome (BS) have many chromosome breaks and a high frequency of sister chromatid exchanges, perhaps in an effort to correct these breaks. The body is small but well-proportioned.kk A somewhat similar disease, the Werner syndrome (WS), is associated with premature aging.11 The Bloom s protein BLM and the WS gene product WRN are both helicases related to E.coli RecQ. Protein BLM colocalizes with replication protein A as discrete foci in the meiotic synaptonemal complex.1 3 Protein WRN also seems to be associated with DNA replication. Defects... 

MutSot binds to G4 DNA with affinity even higher than for the best of its documented substrates in canonical mismatch repair (apparent = 1 nM). This raises the possibility that MutSa directs a pathway for G4 DNA removal. However, downstream factors in this pathway may very well be distinct from those that typically participate in mismatch repair, because binding to G4 DNA is not sensitive to addition of ATP. Interestingly, the RecQ family helicase BLM interacts with and is stimulated by MutSa. This raises the possibility that MutSa might stimulate G4 DNA unwinding, rather than excision of quadruplex structures. 

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