Table S1. Candidate genes selected for the study of
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Table S1. Candidate genes selected for the study of intergenerational instability in families with Machado-Joseph disease Gene name Main activity Accession number Mismatch excision repair (MMR) MSH2 MSH3 NM_000251 Mismatch (MSH2-MSH6) and loop (MSH2MSH3) recognition MSH6 NM_002439 NM_000179 MSH4 NM_002440 Involved in meiotic recombination MSH5 NM_002441 PMS1 Probably involved in the repair of DNA mismatches NM_000534 PMS2 Component of the post-replicative DNA MMR system NM_000535 PMS2P3 MutL homologue NM_005395 PMS2P4 PMS1 homologue NR_046297 MLH1 Heterodimerizes with PMS2 to form MutL alpha NM_000249 MLH3 Probably involved in the repair of DNA mismatches NM_014381 Base excision repair (BER) DNA glycosylases UNG Excises uracil residues from the DNA NM_080911 SMUG1 Recognizes base lesions in the genome and initiates base excision DNA repair NM_014311 MBD4 Mismatch-specific DNA N-glycosylase NM_003925 TDG Hydrolyzes mismatched dsDNA and polynucleotides NM_003211 OGG1 Incises DNA at 8-oxoG residues NM_016821 MUTYH Involved in oxidative DNA damage repair NM_012222 NTHL1 Has both apurinic and/or apyrimidinic endonuclease activity and a DNA Nglycosylase activity NM_002528 MPG Hydrolysis of the deoxyribose N-glycosidic bond to excise 3-methyladenine, and 7methylguanine from the damaged DNA polymer formed by alkylation lesions NM_002434 NEIL1 Recognizes and removes damaged bases of DNA damaged by oxidation or mutagenic agents NM_024608 NEIL2 Has DNA glycosylase activity towards 5hydroxyuracil and other oxidized derivatives of cytosine with a preference for mismatched dsDNA NM_145043 NEIL3 Removes oxidative products of pyrimidines NM_018248 Other BER factors APEX1 Plays a central role in the cellular response to oxidative stress; apurinic/apyrimidinic (AP) endonuclease NM_001641 APEX2 Initiates repair of AP sites NM_014481 LIG3 Interacts with XRCC1 and can correct defective DSB repair and sister chromatid exchange NM_013975 XRCC1 Ligase accessory factor NM_006297 PNKP Part of both NHEJ and BER pathways; converts some DNA breaks to ligatable ends NM_007254 Nucleotide excision repair (NER) XPC Acts as damage sensing and DNA-binding factor component of the XPC complex NM_004628 RAD23B Multiubiquitin chain receptor involved in the modulation of proteasomal degradation NM_002874 CETN2 Plays a fundamental role in microtubuleorganizing center structure and function NM_004344 RAD23A Multiubiquitin chain receptor involved in the modulation of proteasomal degradation; substitutes for HR23B NM_005053 XPA Binds damaged DNA in preincision complex NM_000380 DDB1 Binds to DDB2 to form the UV-damaged DNA-binding protein complex NM_001923 DDB2 Binds to DDB1 to form the UV-damaged DNA-binding protein complex NM_000107 RPA1 Essential in DNA replication, recombination and repair; binds and subsequently stabilizes ssDNA intermediates and thus prevents complementary DNA from reannealing NM_002945 RPA2 Required for the efficient recruitment of the DNA double-strand break (DSB) repair factor RAD51 to chromatin in response to DNA damage NM_002946 RPA3 Required for DNA recombination, repair and replication NM_002947 TFIIH: Catalyzes unwinding in preincision complex ERCC2 NM_000400 5' to 3' DNA helicase ERCC3 NM_000122 GTF2H1 NM_005316 GTF2H3 Component of the core-TFIIH basal transcription factor NM_001516 GTF2H4 NM_001517 GTF2H5 NM_207118 CDK7 Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription NM_001799 CCNH Regulates CDK7 NM_001239 MNAT1 Stabilizes the CCNH-CDK7 complex to form a functional CDK-activating kinase enzymatic complex NM_002431 ERCC5 Single-stranded structure-specific DNA endonuclease (makes the 3'incision in DNA) NM_000123 ERCC1 Endonuclease responsible for the 5' incision DNA binding subunit NM_001983 ERCC4 Structure-specific DNA repair endonuclease responsible for the 5’ incision during repair; involved in homologous recombination that assists in removing interstrand cross-link NM_005236 LIG1 DNA ligase that seals nicks in dsDNA during replication, recombination and repair NM_000234 NER-related ERCC8 Substrate-recognition component of the CSA complex NM_000082 ERCC6 Allows RNA polymerase II-blocking lesions to be removed from the transcribed strand of active genes; upon DNA-binding, it locally modifies DNA conformation by wrapping the DNA around itself, modifying the interface between stalled RNA polymerase II and DNA NM_000124 XAB2 Involved in transcription-coupled repair, transcription and pre-mRNA splicing NM_020196 MMS19 May play a role in NER and RNA polymerase II transcription by interacting with ERCC2 and ERCC3 helicases NM_022362 Other identified genes with a suspected DNA repair function DCLRE1A May be required for DNA interstrand crosslink repair NM_014881 DCLRE1B 5'-3' exonuclease that plays a central role in telomere maintenance and protection during S-phase NM_022836 RPA4 Component of the alternative replication protein A complex, which binds ssDNA NM_013347 RECQL DNA helicase (unwinds ssDNA and dsDNA in a 3'-5' direction) NM_002907 RECQL5 DNA helicase NM_001003715 HELQ 5' to 3' DNA helicase NM_133636 RDM1 Similar to RAD52; binds to DNA and RNA NM_145654 Editing and processing nucleases FEN1 Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair NM_004111 EXO1 5'-3' dsDNA exonuclease with a possible cryptic 3'-5' dsDNA exonuclease activity NM_003686 SPO11 Required for meiotic recombination; mediates NM_012444 DNA cleavage that forms the DSB to initiate meiotic recombination (by similarity) APTX DNA-binding protein involved in ssDNA break repair, DSB repair and BER NM_175073 DNA polymerases (catalytic subunits) POLG Involved in the replication of mtDNA NM_002693 POLD1 Possesses two enzymatic activities: DNA synthesis (polymerase) and an exonucleolytic activity that degrades ssDNA in the 3'- to 5'direction NM_002691 POLE Participates in DNA repair and in chromosomal DNA replication NM_006231 PCNA Auxiliary protein of DNA polymerase delta involved in the control of eukaryotic DNA replication by increasing the polymerase processibility during elongation of the leading strand NM_002592 REV3L Interacts with MAD2L2 to form the error prone DNA polymerase zeta involved in translesion DNA synthesis NM_002912 POLA1 Essential in the initiation of DNA replication NM_016937.3 Other conserved DNA damage response genes RAD1 RAD9A Subunits of PCNA-like sensor of damaged DNA NM_002853 NM_004584 RAD17 Essential for sustained cell growth, maintenance of chromosomal stability NM_002873 TP53 Regulation of the cell cycle NM_000546 ATRIP Required for checkpoint signaling after DNA damage NM_130384 RAD51 Homologous pairing; binds to ssDNA and dsDNA NM_002875 RAD52 Involved in DSB repair; promotes the annealing of complementary ssDNA and stimulates the RAD51 recombinase NM_002879 RAD54L Involved in DNA repair and mitotic NM_003579 Homologous recombination recombination; functions in the recombinational DNA repair pathway RAD50 MRE11A Component of the MRN complex, which plays a central role in DSB repair, DNA recombination, maintenance of telomere integrity and meiosis NM_005732 NM_005590 Interacts with EME1 and EME2 to form a DNA structure-specific endonuclease with substrate preference for branched DNA structures with a 5'-end at the branch nick NM_025128 PRKDC Involved in non-homologous end-joining repair; DNA-dependent protein kinase catalytic subunit NM_006904 WRN Multifunctional enzyme that has both magnesium and ATP-dependent DNAhelicase activity and 3'-5' exonuclease activity towards dsDNA with a 5'-overhang NM_000553.4 ATM Serine/threonine protein kinase that activates checkpoint signaling upon DSBs NM_000051 BLM DNA-helicase; unwinds ssDNA and dsDNA in a 3'-5' direction NM_000057.2 RFC1 May play a role in DNA transcription, regulation and DNA replication and/or repair; can bind ssDNA and dsDNA NM_002913.4 RNaseH1 Endonuclease that specifically degrades the RNA of RNA-DNA hybrids NM_002936.3 DNA2 May function in chromosomal DNA replication (by similarity) NM_001080449.2 PRIM1 Polymerase that synthesizes small RNA primers for the Okazaki fragments made during discontinuous DNA replication NM_000946.2 CLSPN Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication NM_022111.3 CDK7PS Cyclin-dependent kinase 7 pseudogene NG_001572.4 CHEK2 Serine/threonine-protein kinase required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DSBs NM_007194.3 MUS81 Others
