| 2012 |
MMS19 is a member of the cytosolic iron-sulfur protein assembly (CIA) machinery, functioning as part of a CIA targeting complex that specifically interacts with and facilitates iron-sulfur (Fe-S) cluster insertion into apoproteins involved in methionine biosynthesis, DNA replication, DNA repair, and telomere maintenance. MMS19 serves as an adapter between early-acting CIA components (CIAO1, IOP1/NARFL, MIP18/FAM96B) and a subset of cellular Fe-S proteins. |
Co-immunoprecipitation, mass spectrometry, in vitro binding assays, RNAi knockdown with defined cellular phenotypes (Fe-S protein instability) |
Science |
High |
22678361 22678362
|
| 2012 |
MMS19 forms a complex with the CIA proteins CIAO1, IOP1, and MIP18 in the cytoplasm, and also binds directly to multiple nuclear Fe-S proteins involved in DNA metabolism. Knockout of Mms19 in mice causes preimplantation lethality, and loss of MMS19 leads to failure of Fe-S cluster transfer to target proteins and consequent Fe-S protein instability. |
Co-immunoprecipitation, siRNA knockdown, Mms19 knockout mouse model |
Science |
High |
22678361
|
| 2010 |
MMS19 forms a complex with XPD (a TFIIH subunit) and MIP18, FAM96B, CIAO1, and ANT2, designated the MMXD complex, that does not contain other TFIIH subunits. MMS19, MIP18, and XPD localize to the mitotic spindle during mitosis. siRNA knockdown of MMS19, MIP18, or XPD leads to improper chromosome segregation and accumulation of nuclei with abnormal shapes. |
Co-immunoprecipitation, siRNA knockdown, immunofluorescence localization to mitotic spindle |
Molecular Cell |
High |
20797633
|
| 2012 |
MMS19 simultaneously binds CIAO1 and Fe-S proteins, confirming its role as a central CIA component bridging cluster donor proteins and apoprotein recipients. MIP18 also interacts with both CIAO1 and Fe-S proteins by binding Fe-S cluster coordinating regions. ANT2 interacts with Fe-S apoproteins and MMS19 within the CIA complex but not with the individual proteins. |
Co-immunoprecipitation, mass spectrometry-based interactome analysis, in vitro binding |
The Journal of Biological Chemistry |
Medium |
23150669
|
| 2013 |
MMS19, MIP18, and CIAO1 form a tight 'core' CIA complex, while IOP1 is an 'external' component. Deficiency in any core component leads to down-regulation of all core components; IOP1 knockdown does not affect core component levels. MIP18 bridges MMS19 and CIAO1, and MMS19 interacts directly with target Fe-S apoproteins. |
Co-immunoprecipitation (in vivo and in vitro), siRNA knockdown with Western blot quantification |
The Journal of Biological Chemistry |
Medium |
23585563
|
| 2000 |
Human MMS19 (hMMS19) directly interacts with the XPB and XPD helicase subunits of the NER-transcription factor TFIIH, as shown by co-immunoprecipitation. hMMS19 is localized to the nucleus, consistent with a repair function. |
Co-immunoprecipitation, nuclear localization by subcellular fractionation/immunofluorescence |
Nucleic Acids Research |
Medium |
11071939
|
| 2001 |
Human MMS19 interacts with the N-terminal PAS-A/B domain of the nuclear receptor coactivator RAC3 in vivo and in vitro via a conserved C-terminal domain of hMMS19. hMMS19 also interacts with estrogen receptors in a ligand-independent manner but not with retinoic acid receptor or thyroid hormone receptor. Overexpression of full-length hMMS19 enhances ER-mediated transcriptional activation by stimulating AF-1 activity of ERα but not AF-2 activity. |
Co-immunoprecipitation (in vivo and in vitro), overexpression/dominant-negative assays, transcriptional reporter assay |
The Journal of Biological Chemistry |
Medium |
11279242
|
| 1996 |
Yeast MMS19 is required for both nucleotide excision repair (NER) and RNA polymerase II transcription. mms19Δ cell extracts are deficient in Pol II transcription; this defect is corrected by addition of purified TFIIH but not by purified Mms19 protein. Mms19 is not a component of TFIIH or Pol II holoenzyme, but affects their activity as an upstream regulatory element. |
Genetic deletion (mms19Δ), in vitro transcription and NER reconstitution assays, complementation with purified TFIIH |
Molecular and Cellular Biology |
High |
8943333
|
| 2008 |
Yeast Mms19 functions in NER by sustaining adequate cellular concentration of the TFIIH component Rad3 (XPD homologue). In mms19 mutant cells, Rad3 and Ssl2 (XPB homologue) protein levels are significantly reduced (up to 3.5-fold for Rad3). Overexpression of Rad3 from a plasmid restores proficient NER and UV resistance in mms19 mutants, while overexpression of Ssl2 has no effect on repair. |
Genetic deletion and overexpression, Western blot quantification, UV sensitivity complementation assay |
PNAS |
Medium |
18836076
|
| 1997 |
Yeast mms19 deletion mutant cell-free extracts are deficient for NER in vitro, and the mutant is defective in both transcription-coupled and global genome NER in vivo, as demonstrated by inability to remove cyclobutane-pyrimidine dimers from both transcribed and non-transcribed sequences. |
In vitro NER assay, nucleotide-level CPD removal analysis (in vivo strand-specific repair) |
Nucleic Acids Research |
Medium |
9321645
|
| 2006 |
Deletion analysis of MMS19 domains reveals three structurally distinct domains with separable functions: domain A is required for transcription but not NER; domain B is required for NER but not transcription; the C-terminal HEAT repeat domain (domain C) is essential for both NER and transcription functions. |
Domain deletion analysis with complementation of yeast mms19Δ mutant phenotypes (UV sensitivity, thermosensitivity) |
DNA Repair |
Medium |
16797255
|
| 2018 |
Drosophila Mms19 functions in mitosis by allowing CAK (Cdk7/Cyclin H/Mat1) to become fully active as a Cdk1-activating kinase. Mms19 physically and genetically interacts with Xpd, and this interaction prevents Xpd from binding to the CAK complex; Xpd bound to Mms19 frees CAK to phosphorylate Cdk1 and facilitate progression to metaphase. Mitotic defects in Mms19-deficient Drosophila cells can be rescued by overexpression of the CAK complex. |
Genetic rescue (CAK overexpression in Mms19 mutants), physical interaction studies (Co-IP), loss-of-function with mitotic phenotype readout |
Development |
Medium |
29361561
|
| 2020 |
Drosophila Mms19 promotes spindle and astral microtubule (MT) growth, MT stability, and bundling in neural stem cells through two mechanisms: (1) by stimulating the mitotic kinase cascade to trigger localization of the TACC/Msps MT regulatory complex to the centrosome, and (2) by directly binding to microtubules to stimulate MT stability and bundling. |
Loss-of-function with mitotic phenotype quantification, kinase cascade rescue experiments, direct MT-binding assay |
PLoS Genetics |
Medium |
33211700
|
| 2016 |
Human DNA polymerase ε catalytic subunit (POLE1) phosphorylated at serine-1940 interacts with MMS19, but this interaction is not essential: mutation of serine-1940 to alanine caused no defect in proliferation or survival, even after DNA damage. The POLE1-CIAO1 interaction is independent of serine-1940 phosphorylation. |
Co-immunoprecipitation, site-directed mutagenesis, cell survival assay |
DNA Repair |
Medium |
27235625
|
| 2017 |
MMS19 localizes to the inner membrane of mitochondria and participates in mitochondrial DNA (mtDNA) oxidative damage repair. MMS19 knockdown leads to decreased mtDNA copy number, diminished mtDNA repair capacity, and elevated mtDNA common deletion after oxidative stress. Immunoprecipitation-mass spectrometry identified interaction of MMS19 with ANT2, a mitochondrial ATP metabolism protein. |
Subcellular fractionation/mitochondrial localization, siRNA knockdown, immunoprecipitation-mass spectrometry |
Biochemistry and Cell Biology |
Low |
29035693
|
| 2023 |
The transcription factor c-MYC directly activates MMS19 expression in bladder cancer cells, as demonstrated by ChIP and luciferase reporter assays, establishing c-MYC as a transcriptional regulator of MMS19. |
Chromatin immunoprecipitation (ChIP), luciferase reporter assay |
Tissue & Cell |
Low |
37201439
|
| 2024 |
Patients with MMS19 homozygous in-frame deletion mutations develop a lethal neurodegenerative phenotype with microcephaly, brain malformations, and recurrent infections. Patient-derived fibroblasts show profound alterations in proteome, metabolome, and lipidome, consistent with general failure of cytosolic and nuclear Fe-S protein maturation. MMS19 deficiency was confirmed to be detrimental in zebrafish models. |
Genome sequencing, patient fibroblast proteomics/metabolomics/lipidomics, zebrafish knockout model |
Genetics in Medicine |
Medium |
38411040
|