Table 1.
Clusters of simultaneous mutations.
| System | Cause of hypermutation | Hypermutable DNA substrate | Cluster size, (# of mutations) | Selected references |
|---|---|---|---|---|
| Complex mutations | Error by TLS-polymerase | Lesion or local secondary structure | 2–30 nt (2–16) | (49; 68; 85; 86; 123) |
| Mutation showers in Big Blue Mouse | Unknown | Unknown | 1–20 kb (2–6) | (15; 55; 132) |
| E. coli– proliferation in the presence of DNA damaging agent | DNA damage (EMS) | Lesions in dsDNA in front of replication fork | up to 1500 kb (up to 30) | (88) |
| Yeast-subtelomeric | Endogenous (APOBEC) or exogenous (UV, MMS, sufites, H2O2) DNA damage | Long ssDNA at uncapped telomeres | 2–17 kb (2–10) | (17; 24; 25; 36; 140) |
| Yeast – site-specific DSBs | Endogenous (APOBEC) or exogenous (MMS) DNA damage | Long ssDNA created by 5′→3′ resection around DSB or by break-induced replication | 1–170 kb (2–15) | (113; 128; 139; 140) |
| Yeast – proliferation in the presence of DNA damaging agent | Endogenous (APOBEC) or exogenous (MMS) DNA damage | Long ssDNA around DSB (resection and/or BIR), at dysfunctional replication forks or at R-loops | 1–200 kb (2–30) | (63; 108; 128; 129) |
| Retroelements | Endogenous (APOBEC) DNA damage | ssDNA generated by reverse transcription | Entire retroelements, 0.3–10 kb (up to 20–30) | (50; 100; 116) |
| SHM in Ig genes | Endogenous (AID) DNA damage | R-loops or transcription bubbles | 1–4 kb (>2a) | (70; 78; 90; 91; 122) |
| Cancer | Endogenous (AID/APOBEC) DNA damage, other (unidentified) | Long ssDNA | 1–50 kb (2–160) | (3; 14; 83; 91; 98; 99; 104; 107; 108) |
| Human germ line | Unknown | Unknown | 10–100 kb (2–5) | (20; 43; 79) |
a
While multiple mutations accumulate in SHM regions, they may result from AID stimulated mutagenesis in the unknown number of cell generations