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Microcephalin: a causal link between impaired damage response signalling and Microcephaly

journal contribution
posted on 2023-06-07, 13:52 authored by Mark O'DriscollMark O'Driscoll, A. P. Jackson, Penny Jeggo
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.

History

Publication status

  • Published

Journal

Cell Cycle

ISSN

1551-4005

Issue

20

Volume

5

Page range

2339-2344

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2007-03-16

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