Protein: Tonsoku-like protein (Inhibitor of kappa B-related protein) (I-kappa-B-related protein) (IkappaBR) (NF-kappa-B inhibitor-like protein 2) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-like 2) (Q96HA7)
Organism: Homo sapiens (Human)
Function: Component of the MMS22L-TONSL complex, a complex that promotes homologous recombination-mediated repair of double-strand breaks (DSBs) at stalled or collapsed replication forks. The MMS22L-TONSL complex is required to maintain genome integrity during DNA replication. It mediates the assembly of RAD51 filaments on single-stranded DNA (ssDNA): the MMS22L-TONSL complex is recruited to DSBs following histone replacement by histone chaperones and eviction of the replication protein A complex (RPA/RP-A) from DSBs. Following recruitment to DSBs, the TONSL-MMS22L complex promotes recruitment of RAD51 filaments and subsequent homologous recombination. Within the complex, TONSL acts as histone reader, which recognizes and binds newly synthesized histones following their replacement by histone chaperones. Specifically binds histone H4 lacking methylation at 'Lys-20' (H4K20me0) and histone H3.1.
Subcellular location: Nucleus {ECO:0000269|PubMed:21055983, ECO:0000269|PubMed:21055984, ECO:0000269|PubMed:9242696}. Chromosome {ECO:0000269|PubMed:21055983, ECO:0000269|PubMed:21055984, ECO:0000269|PubMed:26527279, ECO:0000269|PubMed:27338793, ECO:0000269|PubMed:29478807}. Cytoplasm {ECO:0000269|PubMed:7738005}. Note=Mainly nuclear (PubMed:21055983, PubMed:21055984). Localizes to DNA damage sites, accumulates at stressed replication forks (PubMed:21055983, PubMed:21055984, PubMed:26527279, PubMed:27338793). Recruited to stalled or collapsed replication forks following histone replacement by histone chaperones ASF1A and the CAF-1 complex: TONSL acts as a histone reader that recognizes and binds newly synthesized histones (PubMed:29478807). {ECO:0000269|PubMed:21055983, ECO:0000269|PubMed:21055984, ECO:0000269|PubMed:26527279, ECO:0000269|PubMed:27338793, ECO:0000269|PubMed:29478807}.
Interaction partners:
- Protein MMS22-like
- Histone H4
- DNA replication licensing factor MCM2
- Histone chaperone ASF1B
- Histone H3.3
- Histone chaperone ASF1A
- FACT complex subunit SSRP1
- Histone H3.1
- WD repeat-containing protein 62
- DNA replication licensing factor MCM6
Sequence:
MSLERELRQLSKAKAKAQRAGQRREEAALCHQLGELLAGHGRYAEALEQHWQELQLRERADDPLGCAVAHRKIGERLAEMEDYPAALQHQHQYLELAHSLRNHTELQRAWATIGRTHLDIYDHCQSRDALLQAQAAFEKSLAIVDEELEGTLAQGELNEMRTRLYLNLGLTFESLQQTALCNDYFRKSIFLAEQNHLYEDLFRARYNLGTIHWRAGQHSQAMRCLEGARECAHTMRKRFMESECCVVIAQVLQDLGDFLAAKRALKKAYRLGSQKPVQRAAICQNLQHVLAVVRLQQQLEEAEGRDPQGAMVICEQLGDLFSKAGDFPRAAEAYQKQLRFAELLDRPGAERAIIHVSLATTLGDMKDHHGAVRHYEEELRLRSGNVLEEAKTWLNIALSREEAGDAYELLAPCFQKALSCAQQAQRPQLQRQVLQHLHTVQLRLQPQEAPETETRLRELSVAEDEDEEEEAEEAAATAESEALEAGEVELSEGEDDTDGLTPQLEEDEELQGHLGRRKGSKWNRRNDMGETLLHRACIEGQLRRVQDLVRQGHPLNPRDYCGWTPLHEACNYGHLEIVRFLLDHGAAVDDPGGQGCEGITPLHDALNCGHFEVAELLLERGASVTLRTRKGLSPLETLQQWVKLYRRDLDLETRQKARAMEMLLQAAASGQDPHSSQAFHTPSSLLFDPETSPPLSPCPEPPSNSTRLPEASQAHVRVSPGQAAPAMARPRRSRHGPASSSSSSEGEDSAGPARPSQKRPRCSATAQRVAAWTPGPASNREAATASTSRAAYQAAIRGVGSAQSRLGPGPPRGHSKALAPQAALIPEEECLAGDWLELDMPLTRSRRPRPRGTGDNRRPSSTSGSDSEESRPRARAKQVRLTCMQSCSAPVNAGPSSLASEPPGSPSTPRVSEPSGDSSAAGQPLGPAPPPPIRVRVQVQDHLFLIPVPHSSDTHSVAWLAEQAAQRYYQTCGLLPRLTLRKEGALLAPQDLIPDVLQSNDEVLAEVTSWDLPPLTDRYRRACQSLGQGEHQQVLQAVELQGLGLSFSACSLALDQAQLTPLLRALKLHTALRELRLAGNRLGDKCVAELVAALGTMPSLALLDLSSNHLGPEGLRQLAMGLPGQATLQSLEELDLSMNPLGDGCGQSLASLLHACPLLSTLRLQACGFGPSFFLSHQTALGSAFQDAEHLKTLSLSYNALGAPALARTLQSLPAGTLLHLELSSVAAGKGDSDLMEPVFRYLAKEGCALAHLTLSANHLGDKAVRDLCRCLSLCPSLISLDLSANPEISCASLEELLSTLQKRPQGLSFLGLSGCAVQGPLGLGLWDKIAAQLRELQLCSRRLCAEDRDALRQLQPSRPGPGECTLDHGSKLFFRRL