Table 1.
Proteins reported to play a role in CFS stability.
| Protein | Function | Role in CFS expression* | Refs |
|---|---|---|---|
| DNA Replication | |||
|
| |||
| MUS81 | Structure-specific endonuclease subunit | M-phase replication | 57–59 |
| EME1 | Structure-specific endonuclease subunit | M-phase replication | 58, 59 |
| RAD52 | Homologous recombination protein | M-phase replication | 55 |
| BLM | RecQ helicase | Suppresses inappropriate recombination | 63 |
| TOP1 | Type I topoisomerase | Relieves torsional stress downstream of replication and transcriptional machineries | 144, 145 |
|
| |||
| Cell Cycle Checkpoints | |||
|
| |||
| ATR | Serine/Threonine kinase | Cell cycle arrest in response to single stranded, unreplicated DNA | 48, 146 |
| ATM | Serine/Threonine kinase | Cell cycle arrest in response to DNA DSBs | 147 |
| CHK1 | Serine/Threonine kinase | Cell cycle arrest in response to DNA damage or unreplicated DNA | 49 |
| Claspin | BRCA1, CHK1 adapter protein | Facilitates the ATR-dependent phosphorylation of BRCA1 and CHK1; Replication fork sensor | 51 |
| HUS1 | Component of the 9-1-1 cell-cycle checkpoint response complex | p53-dependent checkpoint activation and apoptosis | 50 |
| SNM1b | Metallo-β-Lactamase super family protein | Promotes fork collapse, ATR activation | 56 |
|
| |||
| DNA Repair | |||
|
| |||
| RAD51 | Recombinase | Homologous Recombination | 66 |
| BRCA1 | E3 ubiquitin-protein ligase | Genome Surveillance | 65 |
| FANCD2 | Fanconi anemia-linked repair/replication protein | Facilitates Replication | 54, 64 |
| DNA-PK | Serine/Threonine protein kinase | Nonhomologous End-Joining | 66 |
| Ligase IV | ATP-dependent DNA ligase | Nonhomologous End-Joining | 66 |
| XLF | XRCC4-like factor | Nonhomologous End-Joining | 66, 148 |
| WRN | RecQ helicase | DSB repair | 62 |
|
| |||
| Translesion Synthesis | |||
|
| |||
| Pol η | Y family DNA polymerase | DNA synthesis at stalled forks in S phase | 60 |
| Pol κ | Y family DNA polymerase | Replication through repetitive elements | 61 |
| REV3 | Polymerase ζ subunit | G2/M-phase replication | 53 |
|
| |||
| Structural | |||
|
| |||
| SMC1(SMC1A) | Cohesin subunit | Prevents collapse of stalled replications forks | 52 |
*
Proteins have multiple roles in the cell; only roles relevant to CFSs are listed here.
CFS, Common Fragile Site; BLM, Bloom syndrome helicase; TOP1, DNA Topoisomerase 1; ATR, ataxia-telangiectasia and Rad3-related; ATM, Ataxia Telangiectasia Mutated; SNM1B, SNM1 homologue B, also known as APOLLO and DCLRE1B; FANCD2, Fanconi anemia group D2; DNA-PK, DNA-dependent protein kinase; LIG4, DNA Ligase 4; XLF, XRCC4-Like Factor, also known as Non-Homologous End Joining Factor 1 (NHEJ1); WRN, Werner syndrome ATP-dependent helicase; SMC1 (SMC1A), Structural Maintenance of Chromosomes 1A; XRCC4, X-Ray Repair Cross Complementing 4.