5' exonuclease Apollo

Definition:

5'-3' exonuclease that plays a central role in telomere maintenance and protection during S-phase. Participates in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair, thereby ensuring that telomeres do not fuse. Plays a key role in telomeric loop (T loop) formation by being recruited by TERF2 at the leading end telomeres and by processing leading-end telomeres immediately after their replication via its exonuclease activity: generates 3' single-stranded overhang at the leading end telomeres avoiding blunt leading-end telomeres that are vulnerable to end-joining reactions and expose the telomere end in a manner that activates the DNA repair pathways. Together with TERF2, required to protect telomeres from replicative damage during replication by controlling the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Also involved in response to DNA damage: plays a role in response to DNA interstrand cross-links (ICLs) by facilitating double-strand break formation. In case of spindle stress, involved in prophase checkpoint. Possesses beta-lactamase activity, catalyzing the hydrolysis of penicillin G and nitrocefin. Exhibits no activity towards other beta-lactam antibiotic classes including cephalosporins (cefotaxime) and carbapenems (imipenem).

References:

[1]. Seydina M Diene, et al. Human metallo-β-lactamase enzymes degrade penicillin. Sci Rep. 2019 Aug 21;9(1):12173. [Content Brief]

[2]. Marco Anders, et al. Evidence for hSNM1B/Apollo functioning in the HSP70 mediated DNA damage response. Cell Cycle. 2009 Jun 1;8(11):1725-32. [Content Brief]

[3]. Lingling Liu, et al. SNM1B/Apollo interacts with astrin and is required for the prophase cell cycle checkpoint. Cell Cycle. 2009 Feb 15;8(4):628-38. [Content Brief]

[4]. Masamichi Ishiai, et al. DNA cross-link repair protein SNM1A interacts with PIAS1 in nuclear focus formation. Mol Cell Biol. 2004 Dec;24(24):10733-41. [Content Brief]

[5]. Jing Ye, et al. TRF2 and apollo cooperate with topoisomerase 2alpha to protect human telomeres from replicative damage. Cell. 2010 Jul 23;142(2):230-42. [Content Brief]

[6]. Christelle Lenain, et al. The Apollo 5' exonuclease functions together with TRF2 to protect telomeres from DNA repair. Curr Biol. 2006 Jul 11;16(13):1303-10. [Content Brief]

[7]. Ilja Demuth, et al. Endogenous hSNM1B/Apollo interacts with TRF2 and stimulates ATM in response to ionizing radiation. DNA Repair (Amst). 2008 Aug 2;7(8):1192-201. [Content Brief]

[8]. Megan van Overbeek, et al. Apollo, an Artemis-related nuclease, interacts with TRF2 and protects human telomeres in S phase. Curr Biol. 2006 Jul 11;16(13):1295-302. [Content Brief]

[9]. J-B Bae, et al. Snm1B/Apollo mediates replication fork collapse and S Phase checkpoint activation in response to DNA interstrand cross-links. Oncogene. 2008 Aug 28;27(37):5045-56. [Content Brief]

[10]. Ilja Demuth, et al. Human SNM1B is required for normal cellular response to both DNA interstrand crosslink-inducing agents and ionizing radiation. Oncogene. 2004 Nov 11;23(53):8611-8. [Content Brief]

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