InterPro domain: IPR024687

This entry represents the C-terminal domain of MMS19. This domain shares homology with some HEAT repeat sequences. MMS19 is a key component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into apoproteins specifically involved in DNA metabolism and genomic integrity [ 1 , 2 ].

In humans, MMS19 acts as an adapter between early-acting CIA components and a subset of cellular target iron-sulfur proteins such as ERCC2/XPD, FANCJ and RTEL1, thereby playing a key role in nucleotide excision repair (NER) and RNA polymerase II (POL II) transcription [ 3 , 3 ]. It is also part of the MMXD (MMS19-MIP18-XPD) complex, which plays a role in chromosome segregation, probably by facilitating iron-sulfur cluster assembly into ERCC2/XPD [ 3 ].

In budding yeasts, the mms19 mutants were originally isolated in a screening for mutants hypersensitive to the alkylating agent methyl methanesulfonate (MMS) [ 4 ]. Different from human MMS19, Mms19 in budding yeasts (also known as Met18) does not participate directly in NER [ 5 ].

In fission yeast, Mms19 is part of a silencing complex named Rik1-Dos2 complex, which contains Dos2, Rik1, Mms19 and Cdc20. This complex regulates RNA Pol II activity in heterochromatin, and is required for DNA replication and heterochromatin assembly [ 6 ].

1. MMS19 assembles iron-sulfur proteins required for DNA metabolism and genomic integrity. Science 337, 195-9
2. MMS19 links cytoplasmic iron-sulfur cluster assembly to DNA metabolism. Science 337, 243-5
3. MMXD, a TFIIH-independent XPD-MMS19 protein complex involved in chromosome segregation. Mol. Cell 39, 632-40
4. Dual requirement for the yeast MMS19 gene in DNA repair and RNA polymerase II transcription. Mol. Cell. Biol. 16, 6783-93
5. IOP1 protein is an external component of the human cytosolic iron-sulfur cluster assembly (CIA) machinery and functions in the MMS19 protein-dependent CIA pathway. J. Biol. Chem. 288, 16680-9
6. Coordination of DNA replication and histone modification by the Rik1-Dos2 complex. Nature 475, 244-8