CHEK1 – Hereditary Breast Carcinoma

CHK1 (CHEK1) has been investigated for its role in hereditary breast carcinoma (Hereditary breast carcinoma) predisposition through a targeted screen for large genomic rearrangements. In a cohort of 111 Northern Finnish index cases, multiplex ligation-dependent probe amplification did not detect any exonic deletions or amplifications in CHK1, indicating no contribution of such structural variants to familial breast cancer clustering (0 probands) (PMID:20567916). No pathogenic point mutations or segregating variants were reported in this study, and no additional segregation data support CHK1 as a breast cancer susceptibility gene.

Functional studies underscore CHK1's critical role in cell cycle checkpoint activation and DNA damage responses. RNAi and knockout-knockin experiments demonstrate that phosphorylation at serine 317 and 345 is essential for proper G₂/M arrest, chromatin release, and cell survival after genotoxic stress (PMID:17242188), while MCPH1-deficient cells reveal CHK1’s downstream role in ATR-mediated checkpoint maintenance (PMID:16783362). Despite these mechanistic insights into CHK1 function, no disease-specific functional assays link CHK1 perturbation to breast carcinoma predisposition.

References

• Familial Cancer • 2010 • Screening for large genomic rearrangements of the BRIP1 and CHK1 genes in Finnish breast cancer families. PMID:20567916
• Molecular and Cellular Biology • 2007 • Specific role of Chk1 phosphorylations in cell survival and checkpoint activation. PMID:17242188
• Nature Cell Biology • 2006 • Regulation of mitotic entry by microcephalin and its overlap with ATR signalling. PMID:16783362

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