4e45

Structural highlights

Disease

[FANCM_HUMAN] Fanconi anemia. The disease is caused by mutations affecting the gene represented in this entry.

Function

[CENPS_HUMAN] DNA-binding component of the FA core complex involved in DNA damage repair and genome maintenance. Required for optimal chromatin association of the FA core complex. Required for efficient damage-induced monoubiquitination and focus formation of FANCD2. Stabilizes FAAD24, FANCM and STRA13/CENPX in the FA core complex. Plays a role in DNA interstrand cross-linking (ICL) repair and in recovery of replication forks stalled by topoisomerase I-DNA cleavage intermediates induced by camptothecin. Component of the heterotetrameric CENP-T-W-S-X complex that binds and supercoils DNA, and plays an important role in kinetochore assembly. Component of the APITD1/CENPS complex that is essential for the stable assembly of the outer kinetochore. Plays an important role in mitotic progression and chromosome segregation. Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation.^{[1] [2]} [REFERENCE:8] [FANCM_HUMAN] ATPase required for FANCD2 ubiquitination, a key reaction in DNA repair. Binds to ssDNA but not to dsDNA. Recruited to forks stalled by DNA interstrand cross-links, and required for cellular resistance to such lesions.^{[3] [4]} [REFERENCE:7][REFERENCE:8] [CENPX_HUMAN] DNA-binding component of the FA core complex involved in DNA damage repair and genome maintenance. Recruited to forks stalled by DNA interstrand cross-links, and required for cellular resistance to such lesions. Component of the heterotetrameric CENP-T-W-S-X complex that binds and supercoils DNA, and plays an important role in kinetochore assembly. Component of the APITD1/CENPS complex that is essential for the stable assembly of the outer kinetochore. Plays an important role in mitotic progression and chromosome segregation.^{[5] [6]} [REFERENCE:6]

References

1. ↑ Amano M, Suzuki A, Hori T, Backer C, Okawa K, Cheeseman IM, Fukagawa T. The CENP-S complex is essential for the stable assembly of outer kinetochore structure. J Cell Biol. 2009 Jul 27;186(2):173-82. doi: 10.1083/jcb.200903100. Epub 2009 Jul, 20. PMID:19620631 doi:http://dx.doi.org/10.1083/jcb.200903100
2. ↑ Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R. N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi:, 10.1073/pnas.1210303109. Epub 2012 Jul 18. PMID:22814378 doi:http://dx.doi.org/10.1073/pnas.1210303109
3. ↑ Meetei AR, Medhurst AL, Ling C, Xue Y, Singh TR, Bier P, Steltenpool J, Stone S, Dokal I, Mathew CG, Hoatlin M, Joenje H, de Winter JP, Wang W. A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M. Nat Genet. 2005 Sep;37(9):958-63. Epub 2005 Aug 21. PMID:16116422 doi:ng1626
4. ↑ Mosedale G, Niedzwiedz W, Alpi A, Perrina F, Pereira-Leal JB, Johnson M, Langevin F, Pace P, Patel KJ. The vertebrate Hef ortholog is a component of the Fanconi anemia tumor-suppressor pathway. Nat Struct Mol Biol. 2005 Sep;12(9):763-71. Epub 2005 Aug 21. PMID:16116434 doi:10.1038/nsmb981
5. ↑ Amano M, Suzuki A, Hori T, Backer C, Okawa K, Cheeseman IM, Fukagawa T. The CENP-S complex is essential for the stable assembly of outer kinetochore structure. J Cell Biol. 2009 Jul 27;186(2):173-82. doi: 10.1083/jcb.200903100. Epub 2009 Jul, 20. PMID:19620631 doi:http://dx.doi.org/10.1083/jcb.200903100
6. ↑ Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R. N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi:, 10.1073/pnas.1210303109. Epub 2012 Jul 18. PMID:22814378 doi:http://dx.doi.org/10.1073/pnas.1210303109