ERCC6 subfamily

The archetype of the ERCC6 subfamily is the human ERCC6 protein 1, also known as Cockayne Syndrome B (CSB). The S cerevisiae homologue is Rad26p 2.

Although initially regarded as repair proteins due to effects on transcription coupled nucleotide excision repair, more recent hypotheses of the function of ERCC6 has centred on their potential role in assisting transcribing RNA polymerases to either pass or dissociate from blocking DNA lesions 3. The consequent barriers to transcription elongation and sensitivity to DNA damage for non-functional mutants would explain features of Cockayne syndrome. This role is analogous to the role of the non-Snf2 family Mfd DNA translocase from E coli 4.

Interestingly, most higher animal genomes contain 3 separate genes identified as members of the ERCC6 subfamily and one Lodestar subfamily member but only a single gene in the Rad5/16 subfamily. Conversely, fungal genomes typically encode no Lodestar member, a single ERCC6 member and two or more Rad5/16 members. This may reflect divergent strategies for accomplishing transcription-coupled repair.

Although classified in the ERCC6 subfamily, the predicted sequences of the additional animal ERCC6 subfamily genes do diverge from the studied Rad26p/ERCC6.

A number of mutations in the helicase region which result in Cockayne syndrome have been identified and these map to interesting locations in the Snf2 family crystal structures 1, 5. In vitro, purified ERCC6 protein can alter nuclease sensitivity and spacing of nucleosomes in an ATP dependent manner 6. ERCC6 can also bind and negatively supercoil DNA in the presence of non-hydrolysable ATP analogues 7.

names associated with subfamily members
rad26, rhp26, CSB, csb-1, RAD26L
1: Troelstra, C., A. van Gool, et al. (1992). ERCC6, a member of a subfamily of putative helicases, is involved in Cockayne's syndrome and preferential repair of active genes. Cell 71(6): 939-53. PubMed
2: van Gool, A. J., R. Verhage, et al. (1994). RAD26, the functional S. cerevisiae homolog of the Cockayne syndrome B gene ERCC6. Embo J 13(22): 5361-9. PubMed
3: Svejstrup, J. Q. (2003). Rescue of arrested RNA polymerase II complexes. J Cell Sci 116(Pt 3): 447-51. PubMed
4: Park, J. S., M. T. Marr, et al. (2002). E. coli Transcription repair coupling factor (Mfd protein) rescues arrested complexes by promoting forward translocation. Cell 109(6): 757-67. PubMed
5: Durr, H., C. Korner, et al. (2005). X-ray structures of the Sulfolobus solfataricus SWI2/SNF2 ATPase core and its complex with DNA. Cell 121(3): 363-73. PubMed
6: Citterio, E., V. Van Den Boom, et al. (2000). ATP-dependent chromatin remodeling by the Cockayne syndrome B DNA repair-transcription-coupling factor. Mol Cell Biol 20(20): 7643-53. PubMed
7: Beerens, N., J. H. Hoeijmakers, et al. (2005). The CSB protein actively wraps DNA. J Biol Chem 280(6): 4722-9. PubMed