Parallel genome-wide screens identify synthetic viable interactions between the BLM helicase complex and Fanconi anemia

Nature Communications
Martin ModerJoanna I Loizou

Abstract

Maintenance of genome integrity via repair of DNA damage is a key biological process required to suppress diseases, including Fanconi anemia (FA). We generated loss-of-function human haploid cells for FA complementation group C (FANCC), a gene encoding a component of the FA core complex, and used genome-wide CRISPR libraries as well as insertional mutagenesis to identify synthetic viable (genetic suppressor) interactions for FA. Here we show that loss of the BLM helicase complex suppresses FANCC phenotypes and we confirm this interaction in cells deficient for FA complementation group I and D2 (FANCI and FANCD2) that function as part of the FA I-D2 complex, indicating that this interaction is not limited to the FA core complex, hence demonstrating that systematic genome-wide screening approaches can be used to reveal genetic viable interactions for DNA repair defects.

References

May 18, 2001·Nature·J H Hoeijmakers
May 2, 2003·Molecular and Cellular Biology·Amom Ruhikanta MeeteiWeidong Wang
Aug 24, 2005·Nature Structural & Molecular Biology·Georgina MosedaleKetan J Patel
Oct 23, 2009·Nature·Stephen P Jackson, Jiri Bartek
Dec 8, 2009·Science·Jan E CaretteThijn R Brummelkamp
Jan 13, 2010·Molecular Cell·Andrew J Deans, Stephen C West
Apr 5, 2011·Mutation Research·Tae Moon KimPaul Hasty
May 31, 2011·Nature Biotechnology·Jan E CaretteThijn R Brummelkamp
Jul 8, 2011·Nature·Frédéric LangevinKetan J Patel
Aug 26, 2011·Nature·Jan E CaretteThijn R Brummelkamp
Oct 1, 2011·The Journal of Pathology·Gerry P Crossan, Ketan J Patel
Nov 15, 2011·Nature Structural & Molecular Biology·Ivan V RosadoKetan J Patel
May 10, 2013·Nucleic Acids Research·Indrajit ChaudhuryAlexandra Sobeck
Sep 26, 2013·The EMBO Journal·Hocine W MankouriIan D Hickson
Oct 26, 2013·Nature Protocols·F Ann RanFeng Zhang
Oct 29, 2013·Nature Methods·Tilmann BürckstümmerSebastian M B Nijman
Dec 18, 2013·Science·Ophir ShalemFeng Zhang
May 3, 2014·Science·Delphine LarrieuStephen P Jackson
May 6, 2014·Cell Reports·Olga MurinaAlessandro A Sartori
May 17, 2014·Genes & Development·Shriparna SarbajnaStephen C West
Nov 6, 2014·Genome Research·Patrick EssletzbichlerTilmann Bürckstümmer
Oct 17, 2015·Science·Vincent A BlomenThijn R Brummelkamp
Apr 3, 2016·The EMBO Journal·Johanna MichlMadalena Tarsounas
Nov 8, 2016·Nature Chemical Biology·Josep V FormentStephen P Jackson

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Citations

Sep 14, 2018·Cell Cycle·Srijita Dhar, Robert M Brosh
Feb 5, 2019·Critical Reviews in Biochemistry and Molecular Biology·Jihane Basbous, Angelos Constantinou
Jun 13, 2018·Nature Communications·Georgia VelimeziJoanna I Loizou
Feb 8, 2020·Genome Biology·Man-Tat LauG Gregory Neely
Sep 8, 2020·Expert Opinion on Therapeutic Targets·Vivian Weiwen XueWilliam Chi Shing Cho
Feb 28, 2019·Proceedings of the National Academy of Sciences of the United States of America·Katrin UnterhauserEllen L Zechner
Apr 7, 2020·Nature Biotechnology·Thomas Gonatopoulos-PournatzisJason Moffat
Apr 10, 2020·Cellular and Molecular Life Sciences : CMLS·Farah KobaisiXavier Gidrol
Dec 13, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Joshua R HeyzaSteve M Patrick
Mar 30, 2021·Frontiers in Genetics·Ekjot KaurSagar Sengupta
May 14, 2021·Molecular Cell·Michael F SharpWayne Crismani
Jan 21, 2022·Nucleic Acids Research·Christopher B BallDavid H Price

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Methods Mentioned

BETA
gene-trap
flow cytometry
chromosomal aberrations
FACS
reverse transcription PCR
PCR
FCS
Profiler
Illumina

Software Mentioned

Nucleotide BLAST
CellProfiler
ENSEMBL
Picard
bedtools
MAGeCK
Cell Profiler
- VISPR
R
CRISPR Design

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