O'Driscoll, M., Jackson, A. P. and Jeggo, P. A. (2006) Microcephalin: A Causal Link Between Impaired Damage Response Signalling and Microcephaly. Cell Cycle, 5 (20). pp. 2339-2344. ISSN 1551-4005Full text not available from this repository.
Seckel Syndrome (SS) and Primary Microcephaly (MCPH) are disorders exhibiting marked microcephaly with a head circumference less than three standard deviations below the mean. ATR-Seckel Syndrome is conferred by mutations in ataxia and telangiectasia and Rad3 related (ATR), a kinase that activates a DNA damage signalling response. Cell lines from additional SS patients, who are normal for ATR, show defective ATR signalling, suggesting that they carry mutations in other components of the ATR pathway. Primary Microcephaly is distinct from SS since patients display solely microcephaly without accompanying marked growth delay. MCPH1, the first Primary Microcephaly causative gene identified, encodes three BRCT domains, similar to other damage response proteins. Recent studies employing MCPH1 siRNA or exploiting cell lines from MCPH1 patients have shown that MCPH1 functions in the ATR-dependent DNA damage response pathway. Additionally, MCPH1 has a function in the regulation of mitotic entry that is ATR-independent and confers a characteristic phenotype of premature chromosome condensation. Recent studies will be reviewed and their relationship to the aetiology of microcephaly discussed.
|Schools and Departments:||School of Life Sciences|
|Depositing User:||Gee Wheatley|
|Date Deposited:||16 Mar 2007|
|Last Modified:||30 Nov 2012 16:50|