Skip to Main content Skip to Navigation
Journal articles

Cytidine deaminase deficiency impairs sister chromatid disjunction by decreasing PARP-1 activity

Abstract : Bloom Syndrome (BS) is a rare genetic disease characterized by high levels of chromosomal instability and an increase in cancer risk. Cytidine deaminase (CDA) expression is downregulated in BS cells, leading to an excess of cellular dC and dCTP that reduces basal PARP-1 activity, compromising optimal Chk1 activation and reducing the efficiency of downstream checkpoints. This process leads to the accumulation of unreplicated DNA during mitosis and, ultimately, ultrafine anaphase bridge (UFB) formation. BS cells also display incomplete sister chromatid disjunction when depleted of cohesin. Using a combination of fluorescence in situ hybridization and chromosome spreads, we investigated the possible role of CDA deficiency in the incomplete sister chromatid disjunction in cohesin-depleted BS cells. The decrease in basal PARP-1 activity in CDA-deficient cells compromised sister chromatid disjunction in cohesin-depleted cells, regardless of BLM expression status. The observed incomplete sister chromatid disjunction may be due to the accumulation of unreplicated DNA during mitosis in CDA-deficient cells, as reflected in the changes in centromeric DNA structure associated with the decrease in basal PARP-1 activity. Our findings reveal a new function of PARP-1 in sister chromatid disjunction during mitosis.
Document type :
Journal articles
Complete list of metadatas

https://hal-univ-rennes1.archives-ouvertes.fr/hal-01559255
Contributor : Laurent Jonchère <>
Submitted on : Monday, July 10, 2017 - 3:11:28 PM
Last modification on : Tuesday, September 22, 2020 - 3:57:46 AM

Links full text

Identifiers

Citation

Simon Gemble, Géraldine Buhagiar-Labarchède, Rosine Onclercq-Delic, Christian Jaulin, Mounira Amor-Guéret. Cytidine deaminase deficiency impairs sister chromatid disjunction by decreasing PARP-1 activity. Cell Cycle, Taylor & Francis, 2017, 16 (11), pp.1128--1135. ⟨10.1080/15384101.2017.1317413⟩. ⟨hal-01559255⟩

Share

Metrics

Record views

226