BRCA1 A-Complex fine tunes repair functions of BRCA1

Janelle L Harris,Kum Kum Khanna

doi:10.18632/aging.100334

Abstract

BRCA1 A-Complex fine tunes repair functions of BRCA1

Highlights

Germline mutations in BRCA1 increase the risk of breast and ovarian cancer, but the specific pathways driving breast and ovarian cancer development in BRCA1 mutants are currently unclear [1]
The hyperrecombination of K1702M cells is in line with two other studies which found that transient depletion of nonBRCA1 members of the A-Complex caused an increase in recombination, using a similar DR-GFP approach [5, 6]
These studies found that siRNA depletion of BRCC36, one of the A-Complex deubiquitinylating enzymes, increased recombination activity to the same extent as RAP80 depletion[5, 6], seemingly contradicting earlier studies that reported reduced homologous recombination (HR) by depletion of the components of AComplex [13, 18] and the reason for this lack of concordance is unclear

Summary

Introduction

Germline mutations in BRCA1 increase the risk of breast and ovarian cancer, but the specific pathways driving breast and ovarian cancer development in BRCA1 mutants are currently unclear [1]. The hyperrecombination of K1702M cells is in line with two other studies which found that transient depletion of nonBRCA1 members of the A-Complex caused an increase in recombination, using a similar DR-GFP approach [5, 6]. In support of the role of the BRCA1 BRCT domain and the A-Complex in negative regulation of recombination [4,5,6], is the finding that a balance between histone ubiquitinylation by RNF8/ Ubc13 and deubiquitinylation by BRCC36/RAP80 is critical for maintenance of genomic stability [19].

Results

Conclusion