5mkw

Structural highlights

Function

ZRAB3_HUMAN DNA annealing helicase and endonuclease required to maintain genome stability at stalled or collapsed replication forks by facilitating fork restart and limiting inappropriate recombination that could occur during template switching events. Recruited to the sites of stalled DNA replication by polyubiquitinated PCNA and acts as a structure-specific endonuclease that cleaves the replication fork D-loop intermediate, generating an accessible 3'-OH group in the template of the leading strand, which is amenable to extension by DNA polymerase. In addition to endonuclease activity, also catalyzes the fork regression via annealing helicase activity in order to prevent disintegration of the replication fork and the formation of double-strand breaks.^{[1] [2] [3] [4] [5]}

References

1. ↑ Yusufzai T, Kadonaga JT. Annealing helicase 2 (AH2), a DNA-rewinding motor with an HNH motif. Proc Natl Acad Sci U S A. 2010 Dec 7;107(49):20970-3. Epub 2010 Nov 15. PMID:21078962 doi:10.1073/pnas.1011196107
2. ↑ Ciccia A, Nimonkar AV, Hu Y, Hajdu I, Achar YJ, Izhar L, Petit SA, Adamson B, Yoon JC, Kowalczykowski SC, Livingston DM, Haracska L, Elledge SJ. Polyubiquitinated PCNA recruits the ZRANB3 translocase to maintain genomic integrity after replication stress. Mol Cell. 2012 Aug 10;47(3):396-409. doi: 10.1016/j.molcel.2012.05.024. Epub 2012, Jun 14. PMID:22704558 doi:http://dx.doi.org/10.1016/j.molcel.2012.05.024
3. ↑ Yuan J, Ghosal G, Chen J. The HARP-like domain-containing protein AH2/ZRANB3 binds to PCNA and participates in cellular response to replication stress. Mol Cell. 2012 Aug 10;47(3):410-21. doi: 10.1016/j.molcel.2012.05.025. Epub 2012 , Jun 14. PMID:22705370 doi:http://dx.doi.org/10.1016/j.molcel.2012.05.025
4. ↑ Weston R, Peeters H, Ahel D. ZRANB3 is a structure-specific ATP-dependent endonuclease involved in replication stress response. Genes Dev. 2012 Jul 15;26(14):1558-72. doi: 10.1101/gad.193516.112. Epub 2012 Jul, 3. PMID:22759634 doi:http://dx.doi.org/10.1101/gad.193516.112
5. ↑ Badu-Nkansah A, Mason AC, Eichman BF, Cortez D. Identification of a Substrate Recognition Domain in the Replication Stress Response Protein Zinc Finger Ran-binding Domain-containing Protein 3 (ZRANB3). J Biol Chem. 2016 Apr 8;291(15):8251-7. doi: 10.1074/jbc.M115.709733. Epub 2016, Feb 16. PMID:26884333 doi:http://dx.doi.org/10.1074/jbc.M115.709733