±±¾©´óѧ·Ö×ÓÉúÎïѧ±Ê¼Ç A\=:h AQ
µÚÒ»Õ »ùÒòµÄ½á¹¹ 7$^V_{ej
µÚÒ»½Ú »ùÒòºÍ»ùÒò×é ?"L>jr(
Ò»¡¢»ùÒò(gene) Tp9LBF
ÊǺϳÉÒ»ÖÖ¹¦Äܵ°°×»òRNA·Ö×ÓËù±ØÐëµÄÈ«²¿DNAÐòÁУ®
D$j`+`
Ò»¸öµäÐ͵ÄÕæºË»ùÒò°üÀ¨ (V
|
P6C
¢Ù±àÂëÐòÁСªÍâÏÔ×Ó(exon) oVLz7Y[JE
¢Ú²åÈëÍâÏÔ×ÓÖ®¼äµÄ·Ç±àÂëÐòÁСªÄÚºÏ×Ó(intron) o XGf#>keg
¢Û5'-¶ËºÍ3'-¶Ë·Ç·ÒëÇø(UTR) YGxdYwBwf
¢Üµ÷¿ØÐòÁÐ(¿ÉλÓÚÉÏÊöÈýÖÖÐòÁÐÖÐ) A]R"C:o
¾ø´ó¶àÊýÕæºË»ùÒòÊǶÏÁÑ»ùÒò(split-gene)£¬ÍâÏÔ×Ó²»Á¬Ðø¡£ &qo'ge8p
¶þ¡¢»ùÒò×é(genome) V,2O`D%
Ò»Ìض¨ÉúÎïÌåµÄÕûÌ×(µ¥±¶Ìå)ÒÅ´«ÎïÖʵÄ×ܺͣ¬ *aTM3k)Zs
»ùÒò×éµÄ´óСÓÃÈ«²¿DNAµÄ¼î»ù¶Ô×ÜÊý±íʾ¡£ Q>X ;7nt0
ÈË»ùÒò×é3X1 09(30ÒÚbp)£¬¹²±àÂëÔ¼10Íò¸ö»ùÒò¡£ a
8dR.
ÿÖÖÕæºËÉúÎïµÄµ¥±¶Ìå»ùÒò×éÖеÄÈ«²¿DNAÁ¿³ÆΪCÖµ£¬Óë½ø»¯µÄ¸´ÔÓÐÔ²¢²»Ò»ÖÂ(C-value Paradox)¡£ 5|AZ/!rb
ÈËÀà»ùÒò×é¼Æ»®£¨human genome project, HGP£© dAg
a(<K
»ùÒò×éѧ£*****enomics£©,½á¹¹»ùÒò×éѧ£¨structural genomics£©ºÍ¹¦ÄÜ»ùÒò×éѧ£¨functional genomics£©¡£ I]T-}pG
µ°°×ÖÊ×飨proteome£©ºÍµ°°×ÖÊ×éѧ£¨proteomics£© m@jOIt!<
µÚ¶þ½Ú ÕæºËÉúÎï»ùÒò×é H4%wq
Ò»¡¢ÕæºËÉúÎï»ùÒò×éµÄÌص㣺 £¬ q.MM|;_u`
¢ÙÕæºË»ùÒò×éDNAÔÚϸ°ûºËÄÚ´¦ÓÚÒÔºËСÌåΪ»ù±¾µ¥Î»µÄȾɫÌå½á¹¹ÖУ® OD*DHC2rN]
¢ÚÕæºË»ùÒò×éÖУ¬±àÂëÐòÁÐÖ»Õ¼Õû¸ö»ùÒò×éµÄºÜС²¿·Ö(2¡ª3£¥)£¬ VM-J^
¶þ¡¢ÕæºË»ùÒò×éÖÐDNAÐòÁеķÖÀà • I</Nmgf
(Ò»)¸ß¶ÈÖظ´ÐòÁÐ(Öظ´´ÎÊý>lO5) R4{}ZT
ÎÀÐÇDNA(Satellite DNA) fV[xv4D.
(¶þ)ÖжÈÖظ´ÐòÁÐ &9^c-;Vs
1£®ÖжÈÖظ´ÐòÁеÄÌصã
f0:)
¢ÙÖظ´µ¥Î»ÐòÁÐÏàËÆ£¬µ«²»ÍêÈ«Ò»Ñù£¬ #+r-$N.7
¢ÚÉ¢ÔÚ·Ö²¼ÓÚ»ùÒò×éÖУ® k
9s3@S
¢ÛÐòÁеij¤¶ÈºÍ¿½±´Êý·Ç³£²»¾ùÒ»£¬ NbgP,-
¢ÜÖжÈÖظ´ÐòÁÐÒ»°ã¾ßÓÐÖÖÊôÌØÒìÐÔ£¬¿É×÷ΪDNA±ê¼Ç£® `
M\L6o
¢ÝÖжÈÖظ´ÐòÁпÉÄÜÊÇת×ùÔª¼þ(·µ×ù×Ó)£¬ t
6~|T_]
2£®ÖжÈÖظ´ÐòÁеķÖÀà 64zO%F*
¢Ù³¤É¢ÔÚÖظ´ÐòÁÐ(long interspersed repeated segments£®) LINES
vlE#z
¢Ú¶ÌÉ¢ÔÚÖظ´ÐòÁÐ(Short interspersed repeated segments) SINES ^QXUiXzl
SINES£º³¤¶È<500bp£¬¿½±´Êý>105£®ÈçÈËAluÐòÁÐ r}XD{F}"
LINEs£º³¤¶È>1000bp(¿É´ï7Kb),¿½±´Êý104-105£¬ÈçÈËLINEl f *)t<1f
(Èý)µ¥¿½±´ÐòÁÐ(Unique Sequence) w/ZV9"BhE
°üÀ¨´ó¶àÊý±àÂëµ°°×ÖʵĽṹ»ùÒòºÍ»ùÒò¼ä¼ä¸ôÐòÁУ¬ c?wFEADn
Èý¡¢»ùÒò¼Ò×å(gene family) ujDAs%6MZ
Ò»×鹦ÄÜÏàËÆÇÒºËÜÕËáÐòÁоßÓÐͬԴÐԵĻùÒò£®¿ÉÄÜÓÉijһ¹²Í¬
.i`+} @iA
×æÏÈ»ùÒò(ancestral gene)¾Öظ´(duplication)ºÍÍ»±ä²úÉú¡£ $z`
jR*
»ùÒò¼Ò×åµÄÌص㣺 JlGyGr^MD
¢Ù»ùÒò¼Ò×åµÄ³ÉÔ±¿ÉÒÔ´®ÁªÅÅÁÐÔÚÒ»Æð£¬ÐγɻùÒò´Ø(gene cluster)»ò´®ÁªÖظ´»ùÒò(tandemly repeated genes)£¬ÈçrRNA¡¢tRNAºÍ×éµ°°×µÄ»ùÒò£» 7rsrC
¢ÚÓÐЩ»ùÒò¼Ò×åµÄ³ÉÔ±Ò²¿ÉλÓÚ²»Í¬µÄȾɫÌåÉÏ£¬ÈçÖéµ°°×»ùÒò£» GVFD_;j'
¢ÛÓÐЩ³ÉÔ±²»²úÉúÓй¦ÄܵĻùÒò²úÎÕâÖÖ»ùÒò³ÆΪ¼Ù»ùÒò (Pseudogene)£® )v'3pTs2
¦·a1±íʾÓëa1ÏàËƵļٻùÒò£® m@"!=CTKd
¼Ù»ùÒò·ÖÀà¡£¼Ó¹¤¹ýµÄ¼Ù»ùÒò(processed pseudogene)¡£ \QYs(nm?k
µäÐ͵ĻùÒò¼Ò×å ?jb7Oq#[
1£®tRNA»ùÒò q-p4k`]
µ¥±¶ÌåÈË»ùÒò×éÖÐ1300¸ötRNA»ùÒò£¬tRNA»ùÒò´Ø£® D|UDLaz~
2£®rRNA»ùÒò =g?r.;OO
>l00copy£®rRNA»ùÒò´Ø(Öظ´µ¥Ôª28S¡¢18S¡¢5.8s-rRNA) d6~wJ MFl
3£®×éµ°°×»ùÒò l*pCG`@J#
30-40copy£®¶¨Î»£º7q32-q36 .\<
\J|3
×éµ°°×»ùÒò´Ø(Öظ´µ¥Î»£ºH1£¬H2A£¬H2B£¬H3¡¢H4)
{T.$xiR
Ìص㣺ÎÞintron£¬Poly(A)- RNA£® JQI`9$asuC
4£®Öéµ°°×»ùÒò OB5{EILej
¦ÁÀࣺ16p13£¬»ùÒò´Ø(24Kb)£º5¡¯¡ª¦Æ¡ª¦·¦Æ¡ª¦·¦Á1¡ª¦Á2¡ª¦Á1¡ª3¡¯ CYG'W FvZZ
¦ÂÀࣺ11p15£¬»ùÒò´Ø(60Kb)£º5¡¯¡ª ¦Æ¡ªGr¡ªAr¡ª¦·¦Â¡ª¦Ä¡ª¦Â¡ª3¡¯ ?c(f6p?%
ËÄ¡¢³¬»ùÒò¼Ò×å(Supergene family £¬Superfamily) =OhhMAn
ÓÉ»ùÒò¼Ò×åºÍµ¥»ùÒò×é³ÉµÄ´ó»ùÒò¼Ò×壬½á¹¹ÉÏÓг̶Ȳ»µÈµÄͬԴÐÔ£¬µ«¹¦Äܲ»Í¬£® b>;5#OQfn
Îå¡¢ÈËÀà»ùÒò×éÖеÄÖظ´ÐòÁбê¼Ç SyTcp?H
1¡¢A1uÐòÁÐ $eI[3{}X
µ¥±¶ÌåÈË»ùÒò×é50Íò-100Íò¿½±´£¬Æ½¾ùÿ¸ô3-6Kb¾ÍÓÐÒ»¸öAluÐòÁУ¬ "xYMv"X
ÈËA1uÐòÁг¤300bp£º iZ)7%R?5
2X130bpÖظ´ÐòÁУ» @4hxGk=
+31bp¼ä¸ôÐòÁÐ(Öмä)£» )HR'FlxOd
Á½²à7-21bpÕýÏòÖظ´(direct repeats)£¬·µ×ù×Ó? 0d.lF:
AluÐòÁй㷺ɢ²¼ÓÚÈË»ùÒò×飬Լ90%ËÈ¿Ë¡µÄÈË»ùÒòºÏÓÐAluÐòÁÐ c]&(h L
AluÐòÁбêÖ¾¡£ b-%7@j
2¡¢¿É±äÊý´®ÁªÖظ´ • £¬ • 9O P
d'f
Variable number tamdem repeat£¬ VNTR£® >q4nQ/eP
ÓÖ³ÆСÎÀÐÇDNA(minisatellite DNA) ^#XxqVdPk
ÓɶÌÖظ´µ¥Î»(6-40bp)´®ÁªÖظ´(6-100´ÎÒÔÉÏ)¶ø³É£¬¶àλÓÚ»ùÒòµÄ·Ç±àÂëÇø£¬¹ã·º·Ö²¼¡£ (w@|:0t^y[
VNTR¶à̬ÐÔ¡ª·Ö×Ó±ê¼Ç¡ªDNAÖ¸ÎÆͼ£¨fingerprint£©. E$*I.i_m
СÎÀÐÇDNAÍ»±äÓëÖ×Áö£¬H-Ras¡£ \-`L}$
3¡¢¶Ì´®ÁªÖظ´£¨short tandem repeat,STR£© ]';!r20
ÓÖ³Æ΢ÎÀÐÇDNA£¨microstallite DNA£© 7{/qQGL
2-6¸öºËÜÕËá×é³ÉµÄÖظ´µ¥Î»´®ÁªÖظ´(10-60´Î),Á½²àΪÌØÒìµÄµ¥¿½±´ÐòÁУ¬ÈË»ùÒò×éÖÐÿl0kb DNAÐòÁÐÖÁÉÙÒ»¸öSTRÐòÁС£ 2.?:[1g!
{CA)n£¬50£¬000-100£¬000¿½±´£® TkmN.@w_C
ÐÂÒ»´úÒÅ´«±ê¼Ç£¬ÈËÀà»ùÒò×éÑо¿£¬Ö×Áö£¬ÒÅ´«²¡£® tWL9>7]G
µÚÈý½Ú ÏßÁ£Ìå»ùÒò×é !|,=rM9x
ÈËÏßÁ£Ìå»ùÒò×éµÄÌص㣺 %[;<'s5e~
1¡¢ÈËÏßÁ£Ìå»ùÒò×éΪ16£¬569bpµÄË«Á´±Õ»··Ö×Ó£¬Ò»ÌõÁ´ÎªÖØÁ´(HÁ´)£¬Ò»ÌõÁ´ÎªÇáÁ´(LÁ´)£¬Á½ÌõÁ´¾ùÓбàÂ빦ÄÜ£¬Ã¿¸ömtDNA·ÖÓÚ±àÂë13ÖÖµ°°×ÖʺÍ24ÖֽṹRNA(22rRNA£¬2tRNA)£® ]Cbht\Ag"
2¡¢ÏßÁ£ÌåDNAΪĸϵÒÅ´«£® S &cH1QZ
3¡¢½á¹¹»ùÒò²»º¬ÄÚº¬×Ó£¬²¿·ÖÇøÓòÓлùÒòÖصþ£¬Òò´Ë²¡ÀíÐÔmtDNAÍ»±ä¸üÒ×·¢Éú£® /vSFQ}W
4¡¢mtDNAÍ»±äƵÂʸü¸ß£® >PL/>
5¡¢ÏßÁ£ÌåDNAÍ»±äµÄ±íÐͱí´ïÓëºËDNA²»Í¬¡£ )Q~Q.
µÚËÄ½Ú Ï¸¾úºÍ²¡¶¾»ùÒò×é !(l,+@j
Ò»¡¢Ï¸¾ú»ùÒò×éµÄÌص㡣 P@
1D
1£®¹¦ÄÜÏà¹ØµÄ¼¸¸ö½á¹¹»ùÒòÍùÍù´®ÁªÔÚ¡ªÆð£¬ÊÜËüÃÇÉÏÓεĹ²Í¬µ÷¿ØÇø¿ØÖÆ£¬ÐγɲÙ×Ý×ӽṹ£¬ $aG]V-M>
2£®½á¹¹»ùÒòÖÐûÓÐÄÚº¬×Ó£¬Ò²ÎÞÖصþÏÖÏó¡£ z[IG+2
3£®Ï¸¾úDNA´ó²¿·ÖΪ±àÂëÐòÁС£ K#+TCZ,
¶þ¡¢²¡¶¾»ùÒò×éµÄÌصã LP#CA^*S
1£®Ã¿ÖÖ²¡¶¾Ö»ÓÐÒ»ÖÖºËËᣬ»òÕßDNA£¬»òÕßRNA£» rS)7D
2£®²¡¶¾ºËËá´óС²î±ðºÜ´ó£¬3X103Ò»3X106bp£» Z*jhSy
3£®³ýÄ没¶¾Í⣬ËùÓв¡¶¾»ùÒò¶¼Êǵ¥¿½±´µÄ¡£ ~8}"X] 4
4£®´ó²¿·Ý²¡¶¾ºËËáÊÇÓÉÒ»ÌõË«Á´»òµ¥Á´·Ö×Ó(RNA»òDNA)£¬½öÉÙÊýRNA²¡¶¾Óɼ¸¸öºËËáƬ¶Î×é³É£® PY)C=={p
5£®ÕæºË²¡¶¾»ùÒòÓÐÄÚº¬×Ó£¬¶øÊɾúÌ壨¸ÐȾϸ¾úµÄ²¡¶¾£©»ùÒòÖÐÎÞÄÚº¬×Ó£® F''4 j
8
6£®ÓÐÖصþ»ùÒò£® Xqf"Wx(X
µÚÎå½Ú ȾɫÖʺÍȾɫÌå HgduH::\#
ϸ°û·ÖÁѼäÆÚ¡ªÈ¾É«ÖÊ(chromatin) %D e<H*
·ÖÁÑÆÚ¡ªÈ¾É«Ìå(chromosome) qd!$ nr
Ò»¡¢È¾É«ÖʵĻù±¾µ¥Î»¡ªºËСÌå q'",70"\
(Ò»)ºËСÌå(nucleosome)½á¹¹ LvhF@%(9J
DNAÈÆÔÚ×éµ°°×°Ë¾ÛÌå(H2A¡¢H2B¡¢H3¡¢H4¸÷Ò»¶Ô)ºËÐÄÍâ1.8ÖÜ(146bp),ÐγɺËСÌåºËÐÄ¿ÅÁ£¡£ @fbvu_-].
Á½¸öºËСÌåºËÐÄ¿ÅÁ£Ö®¼äÓÐLinker DNA(0-80bp)£¬ BYNOgB1
ºËСÌåºËÐÄ¿ÅÁ£+Linker=ºËСÌå(³¤180-210bp) q\d'}:kfu
ºËС ÌåDNA Ladder£® _aa3Qwx
(¶þ)×éµ°°×(histone)£ºÒ»ÀàСµÄ´øÓзḻÕýµçºÉ<¸»º¬Lys£¬Arg)µÄºËµ°°×£¬ÓëDNAÓиßÇ׺ÍÁ¦£® 7-6_`Q2}Y
×éµ°°×·ÖÀࣺ #^xiv/sV
1£®ºËСÌåºËÐÄ×éµ°°×£¬H2A£¬H2B£¬H3£¬H4¡£·Ö×ÓÁ¿½ÏС(102-135aa) ~)sb\o
×÷ÓãºÅÌÈÆDNAÐγɺËСÌå ¡£ C0KP,JS&
2£®H1×éµ°°×£º½Ï´ó(220aa)£¬×÷ÓãºÓëLinker DNA½áºÏºóÀûÓÚºËСÌåÎȶ¨ºÍ¸ü¸ß¼¶½á¹¹µÄÐγɕ ¡£ ikyvst>O
¶þ¡¢È¾É«Öʵĸ߼¶½á¹¹ P0}uTee
1¡¢30nmȾɫÖÊÏËË¿ £¬ k.
px
2¡¢ñÈ»·½á¹¹(looped domain) ¡£ tUz!]P2BUO
3¡¢Ï¸°û·ÖÁÑÆÚȾɫÌå U%w?muJW
·ÖÁÑÆÚȾɫÌå=Ò»¶Ô½ãÃÃȾɫµ¥Ì壨Chromatid) [eG- &u
ÓÐË¿·ÖÁÑÖÐÆÚ46ÌõȾɫÌå°´´óСºÍÐÎ×´ÅÅÁеĵĹâѧÏÔ΢¾µÍ¼Ïñ³ÆΪÈ˵ÄȾɫÌåºËÐÍ(Karyotype)
1u)I}"{W>
Èý¡¢È¾É«ÌåµÄ½á¹¹ÒªËØ ¡£ ]*I&104{
(Ò»)£®×ÅË¿Á££¨centromere)£ºÏ¸°û·ÖÁÑʱȾɫÌåÓë·Â´¸Ë¿ÏàÁ¬½áµÄ²¿Î»£¬ÎªÈ¾É«ÌåµÄÕý³£·ÖÀëËù±ØÐè¡£ =Lp0i9c
(¶þ)£®¶ËÁ£(telomere)£ºÕæºËÉúÎïÏß״ȾɫÌå·Ö×ÓÄ©¶ËµÄDNAÇøÓò wR>\5z)^
¶ËÁ£DNAµÄÌص㣺 HO&#Lv
1¡¢Óɸ»º¬GµÄ¼òµ¥´®ÁªÖظ´ÐòÁÐ×é³É(³¤´ïÊýkb)£® Ler9~}\D
È˵ĶËÁ£DNAÖظ´ÐòÁУºTTAGGC¡£
7
&l
2¡¢¶ËÁ£µÄÄ©¶Ë¶¼ÓÐÒ»Ìõ12-16¼î»ùµÄµ¥Á´3¡¯¶ËÍ»³ö¡£ Z</$~
T
¶ËÁ£µÄ×÷Ó㺷ÀÖ¹DNAÄ©¶Ë½µ½â£¬±£Ö¤È¾É«ÌåµÄÎȶ¨ÐԺ͹¦ÄÜ 7NoB
£¨Èý£©¡¢¸´ÖÆÔµã 6dq5f?w]
µÚ¶þÕ DNAµÄ¸´ÖÆ¡¢ÐÞ¸´ºÍÖØ×é DFqXZfjm
µÚÒ»½Ú DNAµÄ¸´ÖÆ(DNA Replication) k\zN h<^
Ò»¡¢DNA¸´ÖƵĻù±¾ÌØÐÔ 6M259*ME
1. °ë±£ÁôÐÔ(Semi-Conservative) v3.JG]zLpP
Meselson-StahlʵÑé Tx],-
U
2. Ë«Ïò¸´ÖÆ(Ò»°ã) jJ|O]
v$N
¸´ÖÆÆðʼµã(origin)+Á½²à¸´ÖƲæ=¸´ÖƵ¥Î»(¸´ÖÆ×Ó, Replicon) e@=Bl-
3.°ë²»Á¬ÐøÐÔ(Semi-discontinuous) kAf2g
Ç°µ¼Á´(leading strand)-Á¬ÐøºÏ³É
}$81FSKh
Ëæ´ÓÁ´(Lagging Strand)-²»Á¬Ðø,ÓɸÚÆéƬ¶Î(okazaki fragment)Á¬½Ó¶ø³É. S%g`X
¶þ¡¢DNA¸´ÖƱØÐèµÄ³É·Ý(ÕæºËÉúÎï) 8[2^`g
1.ȾɫÌåDNA¸´ÖƱØÐèÈýÖÖºËÜÕËáÐòÁТٸ´ÖÆÆðµã¢Ú×ÅË¿Á£¢Û¶ËÁ£. :|N5fkhN
2£® RNAÒýÎï(RNA Primer) LUw0MW(Moi
Ò»°ã8-14nt.´øÓÎÀë3'-OHÄ©¶Ë. L[Tr"BW
3.²Î¼ÓDNA¸´ÖƵÄÖ÷ҪøºÍµ°°×ÖÊ SP5/K3t-*
¢Ù DNA¾ÛºÏø(DNA Polymerase) u@[D*c1!H
ÕæºËDNA¸´ÖƵÄÖ÷ҪøDNA Pol a/¦Ä. a&wl-
¹¦ÄÜ:´Ó5'-3'·½ÏòÑÓÉìÓëÄ£°å»¥²¹µÄ×Ó´úÁ´. &kYg
>X
¢ÚÒý·¢Ã¸(Primase) ),dXaP[
ÓëÆäËû¶àÖÖµ°°××é³É¶àµ°°×¸´ºÏÌå-Òý·¢Ìå(Primosome).´ß»¯RNAÒýÎïºÏ³ÉºÍ¸´ÖÆÆðʼ.
d,+d8X
¢ÛDNAÁ¬½Óø(DNA Ligase) 5A:b
\
´ß»¯Ò»¸öË«Á´DNAµÄ5'Á×ËáÓëÁíһ˫Á´DNAµÄ3'-OHÐγÉÁ×Ëá¶þõ¥¼ü. n\wO[l)
¢ÜDNA½âÁ´Ã¸(DNA Helicase),´ò¿ªDNAË«Á´. f{k2sU*uBE
¢ÝÔöֳϸ°ûºË¿¹Ô(Proliferating cell nuclear antigen.PCNA) 5?%(j!p5
¸¨Öú´ß»¯Ç°µ¼Á´ºÏ³É. !NjC+ps]
¢Þ¶ËÁ£Ã¸(Telomerase) ;la(Q~#
Ä©¶Ë¸´ÖÆÎÊÌâ¡£ ?_
}
[@x
¶ËÁ£Ã¸¸ºÔðȾɫÌåÄ©¶Ë(¶ËÁ£)¸´ÖÆ,ÊÇÓÉRNAºÍµ°°×ÖÊ×é³ÉµÄºËÌǺ˵°°×.ÆäÖеÄRNA³É·ÖÊǶËÁ£¸´ÖƵÄÄ£°å.(Òò´Ë¶ËÁ£ÊÇÄæת¼ø) gKn"e|A
×÷ÓÃ:ά³Ö¶ËÁ£³¤¶È. L%U-MOS=
¶ËÁ£Ã¸»îÐÔ¿ÉÓûùÓÚPCRµÄ¡°TRAP¡±£¨Telomerase repeat amplification protocol£©·¨²â¶¨£¨Kim,N et al.,science,266,2011-2014(1994) =<n+AqJ%
¶ËÁ£Óëϸ°ûÊÙÃü¡£ (lTM^3
}
¶ËÁ£¡¢¶ËÁ£Ã¸ÓëÖ×ÁöµÄ¹Øϵ£º¾ø´ó¶àÊý¶ñÐÔÖ×Áö¾ßÓжËÁ£Ã¸»îÐÔµ«¶ËÁ£Ëõ¶Ì£¬µ«Ò²ÓÐÔ¼5%µÄÖ×ÁöÎÞ¶ËÁ£Ã¸»îÐÔÇÒ¶ËÁ£½Ï³¤¡£ ^szCf|SM
¶ËÁ£Ã¸×÷ΪеÄÖ×Áö±êÖ¾ºÍÖ×ÁöÖÎÁưеã. IF$f^$
µÚ¶þ½Ú DNAÐÞ¸´£¨DNA repair£© yzgDdAM
DNAÐÞ¸´ÊÇά³Ö»ùÒò×éÍêÕûÐÔµÄÖØÒª»úÖÆ£¬ÔÚ±£»¤»ùÒò×é±ÜÃâ·¢Éú¿ÉÄܵ¼ÖÂÖ×Áö»òÒÅ´«¼²²¡µÄÍ»±äÖÐÆð¹Ø¼üµÄ×÷Óᣠd7N}-nsB
ÒýÆðDNAËðÉ˵ÄÒòËØ£º _;L9&>!p6
1¡¢ ϸ°ûÄÚÔ´ÐÔËðÉËÒòËØ£º 1^b-
J0
DNA¸´ÖÆ´íÎó£»×Ô·¢ËðÉË°üÀ¨¼î»ù»¥±äÒì¹¹¡¢¼î»ùÍÑ°±£¨C¡úU¡¢A¡úI£©ºÍ¼î»ù¶ªÊ§µÈ£»Ñõ»¯´úл¸±²úÎïÈç»îÐÔÑõÎïÖÊ£¨Reactive oxygen species£¬ROS£©µÄ¹¥»÷µÈ¡£ mp+
%@n.;
2¡¢ »·¾³ÖеÄËðÉËÒòËØ£º q.g<g u]
·øÉ䣨º¬×ÏÍâÏß¡¢XÉäÏߣ©²úÉúÐØÏÙà×शþ¾ÛÌ壻»¯Ñ§Ö°©ÎÑõ»¯ÍÑ°±£¬Í黯¼Á»ò´úл»î»¯ÎïÈç±½²¢ÜÅ¡¢»ÆÇúùËصȲúÉú¼î»ù¼ÓºÏÎ s+h`,gg9
Ò»¡¢¼î»ùÇгýÐÞ¸´(Base excision repair¡¢BER) XGbtmmQG
¸Ã;¾¶ÖÐ×î¹Ø¼üµÄÊDZØÐëͨ¹ýÒ»ÖÖÌÇÜÕø(glycosylase)ÏȳýÈ¥±äÒì¼î»ù(Èç±»Ñõ»¯¡¢Íé»ù»¯»òÍÑ°±µÄ¼î»ù)£¬¸ÃÌÇÜÕø´ß»¯Á¬½ÓËðÉ˼î»ùÓëÍÑÑõºËÌÇÖ®¼äµÄÌÇÜÕ¼üË®½â£¬ÊÍ·ÅÓÎÀë¼î»ù²¢ÔÚDNAÖвúÉúÒ»¸öÈ¥¼î»ùλµã£¬È»ºóÓÉÈ¥àÑßÊ£¯È¥à×à¤(AP)ºËËáÄÚÇÐø¡¢DNA¾ÛºÏøºÍDNAÁ¬½ÓøµÈÀûÓÃÏà¶ÔµÄÒ»ÌõÕý³£Á´ÎªÄ£°å½øÐÐÐÞ²¹ºÏ³É¡£ |Q?IV5%$
BER;¾¶ÖеÄÖØÒªÌÇÜÕø£º xQ-]Iw5
(1)Äòà×à¤DNAÌÇÜÕø(UDG)£¬´ÓDNAÖгýÈ¥Äòà×़î»ù£» {: T'2+OH>
(2)3¡ª¼×»ùÏÙàÑÒ÷(3MeA)DNAÌÇÜÕø£¬¿ÉÐÞ¸´Í黯¼Á²úÉúµÄËðÉË£» 0ua.aL'
(3)¸ºÔðÐÞ¸´DNAÑõ»¯ËðÉ˵ÄÌÇÜÕø£¨ÈçFpg£¯MutM DNAÌÇÜÕø£© A<ur20
BERÊÇÐÞ¸´ÄÚÔ´ÐÔDNAËðÉË(×Ô·¢Ë®½â¡¢Íé»ù»¯ºÍ»îÐÔÑõ¹¥»÷)µÄÖ÷Ҫ;¾¶£¬Òò´Ë¶ÔÓÚ½µµÍ×Ô·¢Í»±äµÄƵÂÊ¡¢·ÀÖ¹Ö×Áö·¢ÉúÓÐÖØÒª×÷Óᣠ?m}vDd
¶þ¡¢ºËÜÕËáÇгýÐÞ¸´(Nucleotide excision repair£¬NER) 4
B"tz!
Ê×ÏÈÓɶà¾ÛÌ帴ºÏÎïʶ±ðËðÉË£¬ÔÙÔÚËðÉ˵ÄÁ½²à½øÐÐÇгý¡£Ëæ×ÅDNAÁ´±»½â¿ª£¬°üº¬ËðÉ˵ĵ¥Á´Æ¬¶ÎÊͷųöÀ´£¬ÁôϵÄȱ¿ÚÓÉDNA¾ÛºÏøÌî²¹£¬DNAÁ¬½Óø·â±Õ¡£¸Ã;¾¶°üÀ¨20ÖÖÒÔÉϵ°°×£¬¿ÉÒÔÐÞ¸´×ÏÍâ·øÉäÓÕµ¼µÄ»·¶¡Íéà×शþ¾ÛÌå(CPD)ºÍ(6¡ª4)¹â²úÎï((6¡ª4)PPs)£¬ÒÔ¼°Ò»Ð©»¯Ñ§ÎïÖʲúÉúµÄ´ó¼ÓºÏÎï¡£ wm%9>mA
%
È˵ÄNERϵͳÓйػùÒò¼°Æäµ°°×ÖʲúÎ﹦ÄÜ¡£ H3H3UIIT_
NERϵͳȱÏÝÓë×ÅÉ«ÐÔ¸ÉƤ²¡£¨Xeroderm pigmentosum,XP£© z
v*
hA/
NER¿ÉÔÙ·ÖΪ¶þÌõ×Ó;¾¶£º ^dJ/>?
1
(1)È«»ùÒò×éÐÞ¸´(Global Genomic repair£¬GGR);¾¶£ºÐÞ¸´Õû¸ö»ùÒò×éÄÚµÄËðÉË£¬ÆäЧÂÊÈ¡¾öÓÚËðÉ˵Ļ¯Ñ§ÌØÐÔ¡¢ËðÉ˲¿Î»µÄDNAÐòÁкÍȾɫÖʽṹ¡£ "\Zsr6y
(2)ת¼źÁªÐÞ¸´(Trancsription¡ªcoupled repair£¬TCR£¬)£ºÌØÒìµØÐÞ¸´»ùÒò×éÖоßÓÐת¼»îÐÔ(¼´±í´ï)µÄ»ùÒòµÄ±»×ªÂ¼DNAÁ´ÉϵÄËðÉË£¬¸Ã;¾¶µÄ ÌصãÊÇÒÀÀµRNA¾ÛºÏøII´ß»¯µÄת¼£¬ÆäÖеÄһЩµ°°×ÊÇÆÕͨת¼Òò×ÓTFIIH µÄÑÇ»ù¡£ XkDjA#nx`
Èý¡¢´íÅäÐÞ¸´(Mismatch repair) kXFgvIpg<
¸ºÔðÐÞ¸´DNA¸´Öƹý³ÌÖÐÓÉÓÚ´íÎó²ôÈë¶ø²úÉúµÄ´íÅä¡£ [nZ3}o
STRÐòÁи´ÖÆ-Ä£°åÁ´µÄ»¬¶¯²úÉúСµÄ»·×´Í»³ö(loop)- Öظ´ÐòÁÐÀ©ÕÅ£¨expansion£©»ò¶ªÊ§£ºÎ¢ÎÀÐDz»Îȶ¨ÐÔ£¨microsatellite instability£© BA4qQCS;5
E coliÖеÄMMR;¾¶ÐèÒªmutS,mutH,mutLºÍuvrD»ùÒò²úÎïºÍÌØÒìÐÔºËËáÍâÇÐø¡¢DNA¾ÛºÏøºÍDNAÁ¬½ÓøµÈ¡£ÔÚ½ÍĸºÍÈËÀàÒѼø¶¨ÁËmutS,mutHµÄ¶àÖÖͬԴÎï¡£ÒÅ´«ÐÔ·ÇÏ¢ÈâÐԽ᳦°©£¨HNPCC£©»ùÒòȱÏÝ¡£ _?x*F?5=
΢ÎÀÐÔ²»Îȶ¨ÓëÖ×Áö¡£ÐµÄÖ×Áö»ùÒòÕï¶Ï±êÖ¾¡£ WZOi,
ËÄ¡¢ÖØ×éÐÞ¸´(Recomhinant repair) LBh|4S$K
ÐÞ¸´DNAµÄÁ½ÌõÁ´¾ùÊÜËðÉ˵IJ¿Î»µÄË«Á´¶ÏÁÑ»òÁ´¼ä½»Á¬¡£ "t$c'`
Further readings: |JC/A;ZH
1 Wood RD£¬DNA repair in eukaryotes£¬Ann Rev Biochem£¬1996£¬65£º135¡ª167 swss#?.se
2 Krokan HE,et a1., DNA glycosylase in the base excision repair of DNA£®Biochem J£¬1997£¬325£º1¡ª16 jQxv`H
3 Vrieling H£¬et a1., Transcription coupled repair and its impact on mutagenesis£¬Mutation Res£¬1998£¬400£º135¡ª142 {dM18;
µÚÈý½Ú ÖØ×é(recombination) JS]6jUB<B
ÖØ×éµÄ±¾ÖÊÊÇ»ùÒòµÄÖØÅÅ»ò½»»».¼´2¸öDNA·Ö×Ó¼ä»òÒ»¸öDNA·Ö×ӵIJ»Í¬²¿Î»¼ä,ͨ¹ý¶ÏÁѺÍÖؽÓ,½»»»DNAƬ¶Î´Ó¶ø¸Ä±ä»ùÒòµÄ×éºÏºÍÐòÁÐ. 9D#"Ey
Ò».ͬԴÖØ×é(Homologous recombination) j"{|* _6E_
Ö¸DNAͬԴÐòÁмäµÄÖØ×é,³£·¢ÉúÓÚÁ½¸ö½Ï³¤µÄͬԴDNAƬ¶Î»òͬԴȾɫÌåÖ®¼ä¡£ ¿Éͨ¹ýͬԴÖØ×齫ÍâÔ´»ùÒò¶¨Î»ÕûºÏµ½Ï¸°û»ùÒò×éÖÐ. /GCI`hx>"
¶þ.ת×ù(transposition) !B5 }`*1D
¿ÉÒƶ¯µÄDNAÔª¼þ(mobile DNA elements) ~>2@55wElp
-ת×ùÔª¼þ(Transposable element).ËüÊÇÖ¸ÄÇЩ¿ÉÔÚDNA·Ö×ÓÄÚ T PEg>[
»òDNA·Ö×Ó¼äתÒƵÄDNAƬ¶Î. e <2?O
ת×ùÔª¼þµÄתÒƹý³Ì-ת×ù TUuw
ת×ùµÄÌصã: E%@,n9T~"
1.ת×ùºóÔÀ´Î»ÖõÄת×ùÔª¼þÐòÁÐÈÔÈ»±£Áô,µ«Í¬Ê±ÓÖ°ÑкϳɵÄDNA ¸´±¾²åÈëµ½ÁíÍâÒ»¸öλµã. ,Dd
)=
2.ת×ù¹ý³ÌÐèҪת×ùø(transposase).Ëü´ß»¯¶ÏÁѺÍÖؽÓÁ½²½Á¬ÐøµÄ ¹ý³Ì(ÐèÒªM2+) SIQ 7oxS4
3.ת×ùÔª¼þ²åÈëλÖõÄÁ½²èÓÐ3-12bpµÄÕýÏòÖظ´ÐòÁÐ(°ÐÐòÁÐ),ËüÊÇÓÉÓÚת×ùø´íλÇиîDNAÔì³ÉµÄ.ÕâÖÖ¶ÌÕýÏòÖظ´ÐòÁÐÊÇ´æÔÚת×ùÔª¼þµÄÌØÕ÷. "
Qj;pqR
ת×ùÔª¼þµÄ·ÖÀà 8@pY:AY
¢Ùת×ù×Ó(transposon):ͨ¹ýDNA¸´ÖƶøתÒƵÄת×ùÔª¼þ. =|_:H$94
¢ÚÄæת×ù×Ó(retroposon)»ò·µ×ù×Ó,ͨ¹ýRNA½×¶ÎʵÏÖתÒƵÄת×ùÔª¼þ (DNA¡ú RNA¡ú DNA¡ú ²åÈëÐÂλµã) E_ #MQ;n
Äæת×ù×ÓÀý:Alu.LINE1.Äæ¼Ù»ùÒò(retro-pseudogene) AJ1(q:P
ת×ùµÄÒÅ´«Ð§Ó¦-µ¼Ö»ùÒòÖØÅÅ¡¢²åÈ롢ȱʧ¡£ lJ1_Zs `
µÚÈýÕ »ùÒò±í´ïµÄµ÷¿Ø JDe
G@N$
»ùÒò±í´ï£ºDNA¡úmRNA¡úµ°°×ÖʵÄÒÅ´«ÐÅÏ¢´«µÝ¹ý³Ì =8:m:Y&|`G
»ùÒò±í´ïµÄµ÷¿Ø >1u!(-A
µÚÒ»½Ú »ùÒòµÄ»î»¯ Qa-]IKOs
»ùÒòµÄ¡°¿ª¹Ø¡±-ȾɫÖʵĻ Jm0o[4
Ò»¡¢»îÐÔȾɫÖʵĽṹ
/E8{:>2
¼äÆÚºËȾɫÖÊ£º 2
u:w
ÒìȾɫÖÊ(heterochromatin)£¬¸ß¶ÈѹËõ(²»×ªÂ¼)£» >#~!03
³£È¾É«ÖÊ(euchromatin)£¬½ÏΪËÉÉ¢£¬ $3.hZx>
³£È¾É«ÖÊÖÐÔ¼10%Ϊ»îÐÔȾɫÖÊ(¸ü¿ª·ÅÊèËÉ)¡£ 2wCTd:e:
»îÐÔȾɫÖÊ¡ú¡û·Ç»îÐÔȾɫÖÊ H5wzzSV!:B
¶þ¡¢»îÐÔȾɫÖʵĽṹÌصã ?5@!r>i=<
(Ò»)DNaseIÃô¸ÐÐÔ 4L<h%
'Zn
ת¼»îÐÔ(»òÓÐDZÔÚת¼»îÐÔ)µÄȾɫÖʶÔDNase I¸üÃô¸Ð£® YhQ;>Ko
DNase I³¬Ãô¸Ðλµã(DNase I HyperSensitive Sites£¬DHSS) Nmu;+{19M
(¶þ)×éµ°°×H3µÄCyS110ÉÏÛÏ»ù±©Â¶£¬ N<XS-XB,
Èý¡¢»îÐÔȾɫÖʽṹµÄÐÎ³É R<wP
O-dX
£¨Ò»)¡¢ºËСÌåλÏà(Phased positioning) /~=W3lhY
1£®ºËСÌåµÄÐýת¶¨Î»(rotational positioning) LEu_RU?
Ö¸ºËСÌåºËÐÄÓëDNAË«ÂÝÐýÔÚ¿Õ¼ä½á¹¹ÖеÄÏ໥¹Øϵ£¬Ö÷Òª°üÀ¨DNAË«ÂÝÐýµÄ´ó¹µÊÇÃæÏò»¹ÊDZ³ÏòºËÐĽṹ£® ¡® Z|l/6L8
2£®ºËСÌåµÄƽÒƶ¨Î»(translational positioning)