The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4

DNA Repair
Paula ClementsKeith W Caldecott

Abstract

Ataxia-oculomotor apraxia 1 (AOA1) is an autosomal recessive neurodegenerative disease that is reminiscent of ataxia-telangiectasia (A-T). AOA1 is caused by mutations in the gene encoding aprataxin, a protein whose physiological function is currently unknown. We report here that, in contrast to A-T, AOA1 cell lines exhibit neither radioresistant DNA synthesis nor a reduced ability to phosphorylate downstream targets of ATM following DNA damage, suggesting that AOA1 lacks the cell cycle checkpoint defects that are characteristic of A-T. In addition, AOA1 primary fibroblasts exhibit only mild sensitivity to ionising radiation, hydrogen peroxide, and methyl methanesulphonate (MMS). Strikingly, however, aprataxin physically interacts in vitro and in vivo with the DNA strand break repair proteins XRCC1 and XRCC4. Aprataxin possesses a divergent forkhead associated (FHA) domain that closely resembles the FHA domain present in polynucleotide kinase, and appears to mediate the interactions with CK2-phosphorylated XRCC1 and XRCC4 through this domain. Aprataxin is therefore physically associated with both the DNA single-strand and double-strand break repair machinery, raising the possibility that AOA1 is a novel DNA damage response-defec...Continue Reading

References

Dec 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·R B Painter, B R Young
Jan 1, 1994·Molecular and Cellular Biology·K W CaldecottL H Thompson
Aug 1, 1997·Current Biology : CB·S E CritchlowS P Jackson
Sep 9, 1999·The Journal of Cell Biology·E P RogakouW M Bonner
Oct 21, 2000·Genes & Development·Y LeeP J McKinnon
Jul 17, 2001·The Journal of Biological Chemistry·Y AndegekoG Rotman
Mar 26, 2002·FEBS Letters·Daniel Durocher, Stephen P Jackson
May 25, 2002·Molecular and Cellular Biology·Xingzhi XuDavid F Stern
Mar 12, 2003·Neurology·C TranchantJ M Warter
Jul 24, 2003·The American Journal of Pathology·Jane StarczynskiPaul G Murray
Sep 25, 2003·Brain : a Journal of Neurology·Isabelle Le BerAlexandra Dürr
Mar 27, 2004·Human Molecular Genetics·Nuri GuevenMartin F Lavin

❮ Previous
Next ❯

Citations

Sep 1, 2005·Current Neurology and Neuroscience Reports·Isabelle Le BerAlexandra Dürr
Sep 23, 2006·Nature Reviews. Cancer·Yves Pommier
Jan 16, 2009·Nature Reviews. Neuroscience·Peter J McKinnon
Oct 11, 2011·Nature Structural & Molecular Biology·Yong GongDa-Cheng Wang
Oct 11, 2011·Nature Structural & Molecular Biology·Percy TumbaleR Scott Williams
Mar 31, 2010·Proceedings of the National Academy of Sciences of the United States of America·Matthew J Cuneo, Robert E London
May 5, 2010·Proceedings of the National Academy of Sciences of the United States of America·Guang-Yao LiC Anne Koch
Apr 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Peter SykoraDavid M Wilson
Mar 26, 2005·The Journal of Biological Chemistry·Heather F SeidleCharles Brenner
Oct 7, 2008·The Journal of Biological Chemistry·Ulrich RassStephen C West
Feb 1, 2013·Brain : a Journal of Neurology·John J Reynolds, Grant S Stewart
May 4, 2005·Nucleic Acids Research·Reto Brem, Janet Hall
Jan 7, 2006·Nucleic Acids Research·Nicolas LévyJosiane Ménissier-de Murcia
Oct 17, 2006·Nucleic Acids Research·Zhiwan Dong, Alan E Tomkinson
Aug 7, 2008·Nucleic Acids Research·Avanti KulkarniDavid M Wilson
Dec 17, 2009·Nucleic Acids Research·Olivier J BecherelMartin F Lavin
Jun 10, 2011·Nucleic Acids Research·Matthew J CuneoRobert E London
Sep 12, 2006·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Osamu Onodera
Dec 24, 2008·Molecular and Cellular Biology·John J ReynoldsKeith W Caldecott
Mar 14, 2007·Molecular and Cellular Biology·Natasha IlesKeith W Caldecott
Jul 9, 2010·Molekuliarnaia biologiia·A I Gaziev, G O Shaĭkhaev
Sep 29, 2005·Journal of Clinical Pathology·A M R Taylor, P J Byrd
Feb 28, 2013·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Brandi L MahaneySusan P Lees-Miller
Jun 4, 2008·Annual Review of Biochemistry·Tom Ellenberger, Alan E Tomkinson
Sep 25, 2007·Annual Review of Genomics and Human Genetics·Peter J McKinnon, Keith W Caldecott
Jan 2, 2013·Genome Integrity·Natasha Tiffany StrandeDale A Ramsden
Jan 20, 2011·EMBO Molecular Medicine·Sherif F El-Khamisy
Mar 5, 2016·Neural Plasticity·Laura NarcisoEugenia Dogliotti
Feb 1, 2015·Progress in Biophysics and Molecular Biology·Matthew J SchellenbergR Scott Williams
Dec 6, 2011·Mechanisms of Ageing and Development·Peter SykoraVilhelm A Bohr
May 10, 2011·Progress in Neurobiology·Dennis Kjølhede JeppesenTinna Stevnsner
Mar 1, 2011·Trends in Biochemical Sciences·Michael WeinfeldJ N Mark Glover
May 10, 2008·DNA Repair·Martin F LavinPadraic Grattan-Smith
May 6, 2008·Mechanisms of Ageing and Development·Sachin Katyal, Peter J McKinnon
Aug 21, 2007·Molecular Aspects of Medicine·Ricky A Sharma, Grigory L Dianov
May 9, 2007·Neuroscience Letters·Makito HiranoSatoshi Ueno

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

Aphasia

Aphasia affects the ability to process language, including formulation and comprehension of language and speech, as well as the ability to read or write. Here is the latest research on aphasia.

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Adenomatous Polyposis Coli

Adenomatous polyposis coli is a protein encoded by the APC gene and acts as a tumor suppressor. Discover the latest research on adenomatous polyposis coli here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis