exonuclease 1 (hExo1, EXO1, EXOI, HEX1)

Function

• 5'->3' double-stranded DNA exonuclease
• cryptic 3'->5' double-stranded DNA exonuclease activity (putative)
• role in DNA mismatch repair to excise mismatch-containing DNA tracts directed by strand breaks located either 5' or 3' to the mismatch
• endonuclease activity against 5' overhanging flap structures similar to those generated by displacement synthesis when DNA polymerase encounters the 5' end of a downstream Okazaki fragment
• required for somatic hypermutation & class switch recombination of immunoglobulin genes
• required for male & female meiosis
• interacts with MLH1-PMS2 heterodimer via MLH1
• interacts with MSH3
• interacts with the MSH2-MSH6 heterodimer via MSH2
  • interaction may increase processivity of 5'->3' exonuclease activity
• interacts with PCNA
  • interaction may both stimulate cryptic 3'->5' exonuclease activity & suppress the 5'->3' exonuclease activity
• interacts with WRN
  • interaction stimulates both the 5'->3' exonuclease activity & cleavage of 5' overhanging flap structures
• interacts with RECQL/RECQ1
  • interaction stimulates cleavage of 5' overhanging flap structures

Structure

• belongs to the XPG/RAD2 endonuclease family, EXO1 subfamily

Compartment

• nucleus
• colocalizes with PCNA to discrete nuclear foci in S-phase

Alternative splicing

named isoforms=2

Expression

• expressed in bone marrow, testis thymus > colon, lymph nodes, ovary, placenta, prostate, small intestine, spleen, stomach
• expressed in fetal liver > fetal brain, heart, kidney, spleen & thymus

Pathology

• germline deletions are not associated with clinically manifested colorectal tumors

Polymorphism

• most naturally occurring variants are not associated with disposition to hereditary non-polyposis colorectal cancer (HNPCC)

More general terms

• exodeoxyribonuclease
• phosphoprotein

Database

• OMIM: https://mirror.omim.org/entry/606063
• UniProt: http://www.uniprot.org/uniprot/Q9UQ84.html