Table 1.
Characterization of XP-E causing mutations
| Patient / Cell line | Allele 1 Amino Acid | Allele 2 Amino Acid♦ | Cancer | UDS | HCR | Biochemistry | Cellular Imaging |
|---|---|---|---|---|---|---|---|
| XP1GO | Thr305Asn | BCC, SCC, M [20] | NR | Reduced [20] | NR | NR | |
| XP37BE& | Arg273His | BCC, SCC [20] |
NR | Reduced [20] |
*DDB1 and Cul4A not detected by co-IP [91, 92] |
No binding to local UV damage; *Part of the DDB-CUL4A-ROC complex [42] |
|
| XP66BE& | Arg273His | M [20] | NR | Reduced [20] |
*DDB1 and Cul4A not detected by co-IP [91, 92] |
No binding to local UV damage; *Part of the DDB-CUL4A-ROC complex [42] |
|
| XP408BE/ GM01389/ GM01646 | Leu350Pro | Asn349del | BCC, SCC, M [20] | 50% [51, 93] |
Reduced [20] | EMSA, no binding activity (E) [51, 93]; DDB1and CUL4A not detected by co-IP [51, 94];no mono-Ub-H2A on chromatin after UVC [94] |
No binding to local UV damage; Fails to recruit DDB1 and Cul4A [44] |
| XP2RO/ GM02415$ | Arg273His | BCC [20, 95] | 40–60% [51, 93, 96] |
NR | EMSA, no binding activity (E) [97] *DDB1 and Cul4A not detected by co-IP [91, 92] |
No binding to local UV damage; *Part of the DDB-CUL4A-ROC complex [42] |
|
| XP3RO/GM02450$ | Arg273His | BCC [20, 95] |
40–60% [51, 96] |
NR |
*DDB1 and Cul4A not detected by co-IP [91, 92] |
No binding to local UV damage; *Part of the DDB-CUL4A-ROC complex [42]; |
|
| XP82TO | Lys244Glu | None (as of 2011) [20, 95] | 44% [51, 96] |
NR | EMSA, no binding activity (E) [28, 93, 97]; Partial binding activity detectable (P) [91]; no histone ubiquitination in nucleosome [91] |
No binding to local UV damage [44, 91]; Slides on DNA in the absence of Mg2+ [50] | |
| XP23PV | Leu235_Lys3 41del | BCC [20, 51] | 65% [51, 93] |
NR | EMSA, no binding activity (E) [51, 93] | No UV-induced chromatin decondensation [44] | |
| XP25PV | Asp307Tyr No change |
BCC, SCC [20, 51] |
50% [51, 93] |
NR | EMSA, no binding activity (E) [51, 93]; DDB1 not detected by co-IP [51] |
No binding to local UV damage; No recruitment of DDB1 and Cul4A [44] |
|
| XP27PV | Lys244X Trp236Valfs10 Leu235_ Lys341del |
BCC, SCC, M [20, 51] | 48% [51] |
NR | EMSA, no binding activity (E) [51, 93]; | NR | |
| Ops1 | Arg313X | BCC, SCC, M [20, 28, 95] |
99–138% [28] |
NR | EMSA, no binding activity (E) [28] DDB1 and Cul4A not detected by co-IP [91] |
NR | |
| XP115BR | Met383fs | None (as of 2016) [7] |
~50% [7] |
NR | NR | NR | |
| XP105BR | Pro357Leu | Arg239Ile | BCC, SCC, M [7] |
~50% [7] |
NR | NR | NR |
| XP98BR | Trp54X | BCC, SCC, M [7] |
~50% [7] |
NR | NR | NR | |
| XP100BR | Splice | BCC [7] |
~50% [7] |
NR | NR | NR |
Abbreviations: BCC, Basal cell carcinoma; SCC, Squamous cell carcinoma; M, Melanoma, UDS, Unscheduled DNA synthesis assay; HCR, Host cell reactivation; Biochemistry includes electrophoretic mobility shift assays (EMSA), western blotting and Co-IP; E: Cell extracts; P: Purified protein; Cellular Imaging examines both recruitment to local damage and FRAP experiments. NR: not reported
&:
Siblings;
$:
Second cousins;
♦
empty boxes for no allele 2 amino acid indicate homozygous mutation;
*
contrasting results from biochemistry and cellular studies