NDLI: The K898E germline variant in the PP1-binding motif of BRCA1 causes defects in DNA Repair

Content Provider	PubMed Central
Author	Chen, Bert Yu-hung Huang, Cheng-hsiang Lin, Ying-hsi Huang, Ching-chun Deng, Chu-xia Hsu, Lih-ching
Copyright Year	2014
Abstract	BRCA1 is a phosphoprotein involved in many biological processes, including transcription, ubiquitination, checkpoint control, homologous recombination, and DNA repair. We have demonstrated that protein phosphatase 1α (PP1α) interacts with BRCA1 via a PP1-binding motif 898KVTF901, and can dephosphorylate multiple serine residues phosphorylated by checkpoint kinases. A K898E germline missense variant in the PP1-binding motif of BRCA1 has been found in an Ashkenazi patient and a non-Ashkenazi Argentinean patient with breast and ovarian cancer, but its clinical significance is still unknown. Here we report that the lysine residue in the PP1-binding motif of BRCA1 is highly conserved across many mammalian species. The K898E mutation interferes with the interaction between BRCA1 and PP1α. Moreover, while the expression of wild-type BRCA1 in Brca1-deficient cells improved cell survival after DNA damage induced by ionizing radiation (IR), expression of BRCA1 K898E proved unable to enhance cell survival. DNA damage repair mechanisms remained defective in these BRCA1 K898E-reconstituted cells, as revealed by the comet assay and IR-induced Rad51 foci formation assay. These results reflect the significance of the interaction between BRCA1 and PP1, and indicate that the K898E variant may render carriers susceptible to DNA damage and malignant transformation.
Related Links	http://dx.doi.org/10.1038/srep05812
Starting Page	5812
File Format	PDF
ISSN	20452322
e-ISSN	20452322
Journal	Scientific Reports
Volume Number	4
Language	English
Publisher	Nature Publishing Group
Publisher Date	2014-07-24
Access Restriction	Open
Rights Holder	Nature Publishing Group
Subject Keyword	Science and technology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

The K898E germline variant in the PP1-binding motif of BRCA1 causes defects in DNA Repair

A PP1-binding motif present in BRCA1 plays a role in its DNA repair function

BARD1 germline variants induce haploinsufficiency and DNA repair defects in neuroblastoma.

Direct DNA binding by Brca1.

Growth Retardation, DNA Repair Defects, and Lack of Spermatogenesis in BRCA1-Deficient Mice

Growth Retardation, DNA Repair Defects, and Lack of Spermatogenesis in BRCA1-Deficient Mice

Bisphenol A impairs the double-strand break repair machinery in the germline and causes chromosome abnormalities

Direct DNA binding by Brca1

The gcm-motif: A novel DNA-binding motif conserved in Drosophila and mammals

The K898E germline variant in the PP1-binding motif of BRCA1 causes defects in DNA Repair

Similar Documents

The K898E germline variant in the PP1-binding motif of BRCA1 causes defects in DNA Repair

A PP1-binding motif present in BRCA1 plays a role in its DNA repair function

BARD1 germline variants induce haploinsufficiency and DNA repair defects in neuroblastoma.

Direct DNA binding by Brca1.

Growth Retardation, DNA Repair Defects, and Lack of Spermatogenesis in BRCA1-Deficient Mice

Growth Retardation, DNA Repair Defects, and Lack of Spermatogenesis in BRCA1-Deficient Mice

Bisphenol A impairs the double-strand break repair machinery in the germline and causes chromosome abnormalities

Direct DNA binding by Brca1

The gcm-motif: A novel DNA-binding motif conserved in Drosophila and mammals

The K898E germline variant in the PP1-binding motif of BRCA1 causes defects in DNA Repair