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Structure of PAXX

Structural highlights

3wtf is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.451Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PAXX_HUMAN Non-essential DNA repair protein involved in DNA non-homologous end joining (NHEJ); participates in double-strand break (DSB) repair and V(D)J recombination (PubMed:25574025, PubMed:25670504, PubMed:25941166, PubMed:27705800). May act as a scaffold required for accumulation of the Ku heterodimer, composed of XRCC5/Ku80 and XRCC6/Ku70, at double-strand break sites and promote the assembly and/or stability of the NHEJ machinery (PubMed:25574025, PubMed:25670504, PubMed:25941166). Involved in NHEJ by promoting the ligation of blunt-ended DNA ends (PubMed:27703001). Together with NHEJ1/XLF, collaborates with DNA polymerase lambda (POLL) to promote joining of non-cohesive DNA ends (PubMed:30250067, PubMed:25670504). Constitutes a non-essential component of classical NHEJ: has a complementary but distinct function with NHEJ1/XLF in DNA repair (PubMed:27705800). Able to restrict infection by herpesvirus 1 (HSV-1) via an unknown mechanism (PubMed:29144403).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

XRCC4 and XLF are two structurally related proteins that function in DNA double-strand break (DSB) repair. Here, we identify human PAXX (PAralog of XRCC4 and XLF, also called C9orf142) as a new XRCC4 superfamily member and show that its crystal structure resembles that of XRCC4. PAXX interacts directly with the DSB-repair protein Ku and is recruited to DNA-damage sites in cells. Using RNA interference and CRISPR-Cas9 to generate PAXX(-/-) cells, we demonstrate that PAXX functions with XRCC4 and XLF to mediate DSB repair and cell survival in response to DSB-inducing agents. Finally, we reveal that PAXX promotes Ku-dependent DNA ligation in vitro and assembly of core nonhomologous end-joining (NHEJ) factors on damaged chromatin in cells. These findings identify PAXX as a new component of the NHEJ machinery.

DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair.,Ochi T, Blackford AN, Coates J, Jhujh S, Mehmood S, Tamura N, Travers J, Wu Q, Draviam VM, Robinson CV, Blundell TL, Jackson SP Science. 2015 Jan 9;347(6218):185-188. doi: 10.1126/science.1261971. PMID:25574025^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ochi T, Blackford AN, Coates J, Jhujh S, Mehmood S, Tamura N, Travers J, Wu Q, Draviam VM, Robinson CV, Blundell TL, Jackson SP. DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair. Science. 2015 Jan 9;347(6218):185-188. doi: 10.1126/science.1261971. PMID:25574025 doi:http://dx.doi.org/10.1126/science.1261971
↑ Xing M, Yang M, Huo W, Feng F, Wei L, Jiang W, Ning S, Yan Z, Li W, Wang Q, Hou M, Dong C, Guo R, Gao G, Ji J, Zha S, Lan L, Liang H, Xu D. Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway. Nat Commun. 2015 Feb 11;6:6233. doi: 10.1038/ncomms7233. PMID:25670504 doi:http://dx.doi.org/10.1038/ncomms7233
↑ Craxton A, Somers J, Munnur D, Jukes-Jones R, Cain K, Malewicz M. XLS (c9orf142) is a new component of mammalian DNA double-stranded break repair. Cell Death Differ. 2015 Jun;22(6):890-7. PMID:25941166 doi:10.1038/cdd.2015.22
↑ Chang HHY, Watanabe G, Gerodimos CA, Ochi T, Blundell TL, Jackson SP, Lieber MR. Different DNA End Configurations Dictate Which NHEJ Components Are Most Important for Joining Efficiency. J Biol Chem. 2016 Nov 18;291(47):24377-24389. PMID:27703001 doi:10.1074/jbc.M116.752329
↑ Tadi SK, Tellier-Lebègue C, Nemoz C, Drevet P, Audebert S, Roy S, Meek K, Charbonnier JB, Modesti M. PAXX Is an Accessory c-NHEJ Factor that Associates with Ku70 and Has Overlapping Functions with XLF. Cell Rep. 2016 Oct 4;17(2):541-555. PMID:27705800 doi:10.1016/j.celrep.2016.09.026
↑ Trigg BJ, Lauer KB, Fernandes Dos Santos P, Coleman H, Balmus G, Mansur DS, Ferguson BJ. The Non-Homologous End Joining Protein PAXX Acts to Restrict HSV-1 Infection. Viruses. 2017 Nov 16;9(11):342. PMID:29144403 doi:10.3390/v9110342
↑ Craxton A, Munnur D, Jukes-Jones R, Skalka G, Langlais C, Cain K, Malewicz M. PAXX and its paralogs synergistically direct DNA polymerase λ activity in DNA repair. Nat Commun. 2018 Sep 24;9(1):3877. PMID:30250067 doi:10.1038/s41467-018-06127-y
↑ Ochi T, Blackford AN, Coates J, Jhujh S, Mehmood S, Tamura N, Travers J, Wu Q, Draviam VM, Robinson CV, Blundell TL, Jackson SP. DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair. Science. 2015 Jan 9;347(6218):185-188. doi: 10.1126/science.1261971. PMID:25574025 doi:http://dx.doi.org/10.1126/science.1261971